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310 KiB

Open AccessArticle

Enhancement or Reduction of Sonochemical Activity of Pulsed Ultrasound Compared to Continuous Ultrasound at 20 kHz?

by Yujing Sun and Xingqian Ye

Molecules 2013, 18(5), 4858-4867; https://doi.org/10.3390/molecules18054858 - 24 Apr 2013

Cited by 10 | Viewed by 4550

Abstract

Little is known about the efficacy of pulsed ultrasound compared with continuous ultrasound. Previous studies on the efficacy of pulsed ultrasound were not systematic and gave different results. In this study, the effects of pulse length, pulse interval, pulse length × pulse intervals, [...] Read more.

Little is known about the efficacy of pulsed ultrasound compared with continuous ultrasound. Previous studies on the efficacy of pulsed ultrasound were not systematic and gave different results. In this study, the effects of pulse length, pulse interval, pulse length × pulse intervals, and treatment time on sonochemical activity were investigated using a simple oxidation of iodide method and a comparison of the efficacy of pulsed ultrasound and continuous ultrasound is made. The results showed that the main factor in the efficacy of pulsed ultrasound was pulse length when pulse length varied from 0.1 to 1 s. However, the main factors were pulse length, the pulse length × pulse interval, and pulse interval when pulse length varied from 1 to 9 s. Pulsed ultrasound had no effect when the pulse length was 0.1 s; however, the sonochemical activity of pulsed ultrasound decreased compared to continuous ultrasound as the pulse length varied from 0.1 to 1 s. The sonochemical activity of pulsed ultrasound either increased or decreased compared to continuous ultrasound when pulse length varied from 1 to 9 s, but the increase or decrease had no clear trend. The sonochemical activity was constant at T_on/T_off = 2 s/2 s and slightly decreased at T_on/T_off = 3 s/2 s with time, whereas the sonochemical activity of continuous ultrasound significantly decreased with time. Enhancement or reduction of sonochemical activity of pulsed ultrasound compared to continuous ultrasound depended on the pulse length and pulse interval. Full article

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276 KiB

Open AccessArticle

Two New Oleanane-Type Triterpenes Isolated from Japanese Post-Fermented Tea Produced by Anaerobic Microbial Fermentation

by Yong-Lin Huang, Sachi Nagai, Takashi Tanaka, Yosuke Matsuo, Yoshinori Saito and Isao Kouno

Molecules 2013, 18(5), 4868-4875; https://doi.org/10.3390/molecules18054868 - 24 Apr 2013

Cited by 15 | Viewed by 6077

Abstract

Four triterpenes were isolated from a traditional Japanese tea product produced by anaerobic microbial fermentation of heated green tea leaves (Camellia sinensis). Two of the compounds were novel and characterized by spectroscopic investigation to be 13,26-epoxy-3β,11α-dihydroxyolean-12-one and 3β,11α,13β-trihydroxyolean-12-one. Two known triterpenes were identified [...] Read more.

Four triterpenes were isolated from a traditional Japanese tea product produced by anaerobic microbial fermentation of heated green tea leaves (Camellia sinensis). Two of the compounds were novel and characterized by spectroscopic investigation to be 13,26-epoxy-3β,11α-dihydroxyolean-12-one and 3β,11α,13β-trihydroxyolean-12-one. Two known triterpenes were identified as taraxastane-3β,20β-diol and taraxastane-3β,20α-diol. These triterpenes were not detected in the original green tea leaves. Full article

(This article belongs to the Section Natural Products Chemistry)

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369 KiB

Open AccessArticle

Anti-Oxidative and Anti-Proliferative Activity on Human Prostate Cancer Cells Lines of the Phenolic Compounds from Corylopsis coreana Uyeki

by Manh Heun Kim, Sung Yi Ha, Myeong Hwan Oh, Han Hyuk Kim, So Ra Kim and Min Won Lee

Molecules 2013, 18(5), 4876-4886; https://doi.org/10.3390/molecules18054876 - 24 Apr 2013

Cited by 21 | Viewed by 6309

Abstract

Fifteen phenolic compounds, including three caffeoyl derivatives, four gallotannins, three ellagitannins and five flavonoids, were isolated from an 80% MeOH extract of the leaves of Corylopsis coreana Uyeki (Korean winter hazel; CL). The anti-oxidative activities [1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase [...] Read more.

Fifteen phenolic compounds, including three caffeoyl derivatives, four gallotannins, three ellagitannins and five flavonoids, were isolated from an 80% MeOH extract of the leaves of Corylopsis coreana Uyeki (Korean winter hazel; CL). The anti-oxidative activities [1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase superoxide scavenging activities (NBT)] and the anti-proliferative activity on human prostate cancer cell lines (DU145 and LNCaP) were also evaluated. Full article

(This article belongs to the Section Natural Products Chemistry)

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266 KiB

Open AccessArticle

Zero-Point Corrections for Isotropic Coupling Constants for Cyclohexadienyl Radical, C₆H₇ and C₆H₆Mu: Beyond the Bond Length Change Approximation

by Bruce S. Hudson and Suzanne K. Chafetz

Molecules 2013, 18(5), 4906-4916; https://doi.org/10.3390/molecules18054906 - 25 Apr 2013

Cited by 7 | Viewed by 6186

Abstract

Zero-point vibrational level averaging for electron spin resonance (ESR) and muon spin resonance (µSR) hyperfine coupling constants (HFCCs) are computed for H and Mu isotopomers of the cyclohexadienyl radical. A local mode approximation previously developed for computation of the effect of replacement of [...] Read more.

Zero-point vibrational level averaging for electron spin resonance (ESR) and muon spin resonance (µSR) hyperfine coupling constants (HFCCs) are computed for H and Mu isotopomers of the cyclohexadienyl radical. A local mode approximation previously developed for computation of the effect of replacement of H by D on ¹³C-NMR chemical shifts is used. DFT methods are used to compute the change in energy and HFCCs when the geometry is changed from the equilibrium values for the stretch and both bend degrees of freedom. This variation is then averaged over the probability distribution for each degree of freedom. The method is tested using data for the methylene group of C₆H₇, cyclohexadienyl radical and its Mu analog. Good agreement is found for the difference between the HFCCs for Mu and H of CHMu and that for H of CHMu and CH₂ of the parent radical methylene group. All three of these HFCCs are the same in the absence of the zero point average, a one-parameter fit of the static HFCC, a(0), can be computed. That value, 45.2 Gauss, is compared to the results of several fixed geometry electronic structure computations. The HFCC values for the ortho, meta and para H atoms are then discussed. Full article

(This article belongs to the Collection Isotope Effects)

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674 KiB

Open AccessArticle

A Preliminary Study of the Effect of DBD Plasma and Osmolytes on T98G Brain Cancer and HEK Non-Malignant Cells

by Nagendra Kumar Kaushik, Pankaj Attri, Neha Kaushik and Eun Ha Choi

Molecules 2013, 18(5), 4917-4928; https://doi.org/10.3390/molecules18054917 - 25 Apr 2013

Cited by 52 | Viewed by 7335

Abstract

Non-thermal plasmas are emerging as a novel tool for the treatment of living tissues for biological and medical purpose. In this study, we described the effect of 4 min dielectric barrier discharge (DBD) plasma on both T98G cancer and HEK normal cell lines [...] Read more.

Non-thermal plasmas are emerging as a novel tool for the treatment of living tissues for biological and medical purpose. In this study, we described the effect of 4 min dielectric barrier discharge (DBD) plasma on both T98G cancer and HEK normal cell lines in the presence of different concentrations of osmolytes. This treatment strategy shows a specific inhibitory effect of a 240 s plasma exposure in the presence of osmolytes against T98G brain cancer cells only, but not on HEK normal cells. Based on these interesting properties of osmolytes, a non-thermal plasma appears to be a potential anticancer treatment strategy for different kinds of cancers in the presence of osmolytes. Full article

(This article belongs to the Section Medicinal Chemistry)

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422 KiB

Open AccessArticle

Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease

by Karla Ramírez-Gualito, Monique Richter, Manolis Matzapetakis, David Singer and Stefan Berger

Molecules 2013, 18(5), 4929-4941; https://doi.org/10.3390/molecules18054929 - 26 Apr 2013

Viewed by 7259

Abstract

Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer’s disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly [...] Read more.

Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer’s disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau_229-237[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B_241-255 originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible. Full article

(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)

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209 KiB

Open AccessArticle

Phenolic Constituents, Antioxidant and Preliminary Antimycoplasmic Activities of Leaf Skin and Flowers of Aloe vera (L.) Burm. f. (syn. A. barbadensis Mill.) from the Canary Islands (Spain)

by Aroa López, Miguel Suárez De Tangil, Orestes Vega-Orellana, Ana S. Ramírez and Milagros Rico

Molecules 2013, 18(5), 4942-4954; https://doi.org/10.3390/molecules18054942 - 26 Apr 2013

Cited by 92 | Viewed by 22920

Abstract

The methanol extracts of leaf skins and flowers of Aloe vera from the Canary Islands were analyzed for their phenolic profiles and screened for their antioxidant and antimycoplasmic activities. The use of reversed phase high performance liquid chromatography (RP-HPLC) allowed the identification of [...] Read more.

The methanol extracts of leaf skins and flowers of Aloe vera from the Canary Islands were analyzed for their phenolic profiles and screened for their antioxidant and antimycoplasmic activities. The use of reversed phase high performance liquid chromatography (RP-HPLC) allowed the identification of 18 phenolic constituents. Leaf skin extracts were characterized by the abundance of catechin, sinapic acid and quercitrin. Gentisic acid, epicatechin and quercitrin were the most prominent phenolic compounds of the flowers. The in vitro antioxidant activities determined by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric antioxidant reducing power (FRAP) assays revealed that both extracts exhibited antioxidant activity, being the leaf skin extract the most active fraction. The leaf skin extract was also found to be active against the microbial strains tested. Therefore, A. vera extracts from leaf skin and flowers can be considered as good natural antioxidant sources. Full article

(This article belongs to the Special Issue Phytochemicals: Analytical and Medicinal Chemistry)

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778 KiB

Open AccessArticle

2'-Deoxythymidine Adducts from the Anti-HIV Drug Nevirapine

by Alexandra M. M. Antunes, Benjamin Wolf, M. Conceição Oliveira, Frederick A. Beland and M. Matilde Marques

Molecules 2013, 18(5), 4955-4971; https://doi.org/10.3390/molecules18054955 - 26 Apr 2013

Cited by 8 | Viewed by 7698

Abstract

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used against HIV-1. Currently, NVP is the most widely used anti-HIV drug in developing countries, both in combination therapy and to prevent mother-to-child transmission of HIV. Despite its efficacy against HIV, NVP produces a [...] Read more.

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used against HIV-1. Currently, NVP is the most widely used anti-HIV drug in developing countries, both in combination therapy and to prevent mother-to-child transmission of HIV. Despite its efficacy against HIV, NVP produces a variety of toxic responses, including hepatotoxicity and skin rash. It is also associated with increased incidences of hepatoneoplasias in rodents. In addition, epidemiological data suggest that NNRTI use is a risk factor for non-AIDS-defining cancers in HIV-positive patients. Current evidence supports the involvement of metabolic activation to reactive electrophiles in NVP toxicity. NVP metabolism includes oxidation to 12-hydroxy-NVP; subsequent Phase II sulfonation produces an electrophilic metabolite, 12-sulfoxy-NVP, capable of reacting with DNA to yield covalent adducts. Since 2’-deoxythymidine (dT) adducts from several alkylating agents are regarded as having significant mutagenic/carcinogenic potential, we investigated the formation of NVP-dT adducts under biomimetic conditions. Toward this goal, we initially prepared and characterized synthetic NVP-dT adduct standards using a palladium-mediated Buchwald-Hartwig coupling strategy. The synthetic standards enabled the identification, by LC-ESI-MS, of 12-(2'-deoxythymidin-N3-yl)-nevirapine (N3-NVP-dT) in the enzymatic hydrolysate of salmon testis DNA reacted with 12-mesyloxy-NVP, a synthetic surrogate for 12-sulfoxy-NVP. N3-NVP-dT, a potentially cytotoxic and mutagenic DNA lesion, was also the only dT-specific adduct detected upon reaction of dT with 12-mesyloxy-NVP. Our data suggest that N3-NVP-dT may be formed in vivo and play a role in the hepatotoxicity and/or putative hepatocarcinogenicity of NVP. Full article

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1705 KiB

Open AccessArticle

A Lead (II) 3D Coordination Polymer Based on a Marine Cyclic Peptide Motif

by Subrata Chakraborty, Pooja Tyagi, Dar-Fu Tai, Gene-Hsiang Lee and Shie-Ming Peng

Molecules 2013, 18(5), 4972-4985; https://doi.org/10.3390/molecules18054972 - 26 Apr 2013

Cited by 10 | Viewed by 6449

Abstract

The crystal structure of a naturally occurring cyclic tetrapeptide cyclo(Gly-L-Ser-L-Pro-L-Glu) [cyclo(GSPE)] was obtained. The conformation of synthesized cyclo(GSPE) fixes the coordination to lead ion in a 1:1 ratio. This cyclo(GSPE)-Pb complex was constructed as an asymmetric 3D network [...] Read more.

The crystal structure of a naturally occurring cyclic tetrapeptide cyclo(Gly-L-Ser-L-Pro-L-Glu) [cyclo(GSPE)] was obtained. The conformation of synthesized cyclo(GSPE) fixes the coordination to lead ion in a 1:1 ratio. This cyclo(GSPE)-Pb complex was constructed as an asymmetric 3D network in the crystalline state. The polymerization of a heavy metal ion with a rigid asymmetric cyclic tetrapeptide represents the first example of a new class of macrocyclic complexes. Full article

(This article belongs to the Special Issue Macrocyclic Chemistry)

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281 KiB

Open AccessArticle

Spectroscopic Studies of Amino Acid Ionic Liquid-Supported Schiff Bases

by Paula Ossowicz, Ewa Janus, Grzegorz Schroeder and Zbigniew Rozwadowski

Molecules 2013, 18(5), 4986-5004; https://doi.org/10.3390/molecules18054986 - 29 Apr 2013

Cited by 32 | Viewed by 7176

Abstract

Amino acid ionic liquid-supported Schiff bases, derivatives of salicylaldehyde and various amino acids (L-threonine, L-valine, L-leucine, L-isoleucine and L-histidine) have been investigated by means of various spectroscopic techniques (NMR, UV-Vis, IR, MS) and deuterium isotope effects on ¹³C-NMR chemical shifts. The results [...] Read more.

Amino acid ionic liquid-supported Schiff bases, derivatives of salicylaldehyde and various amino acids (L-threonine, L-valine, L-leucine, L-isoleucine and L-histidine) have been investigated by means of various spectroscopic techniques (NMR, UV-Vis, IR, MS) and deuterium isotope effects on ¹³C-NMR chemical shifts. The results have shown that in all studied amino acid ionic liquid-supported Schiff bases (except the L-histidine derivative) a proton transfer equilibrium exists and the presence of the COO⁻ group stabilizes the proton transferred NH-form. Full article

(This article belongs to the Collection Isotope Effects)

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538 KiB

Open AccessArticle

Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase

by Norka B. H. Lozano, Rafael F. Oliveira, Karen C. Weber, Kathia M. Honorio, Rafael V. Guido, Adriano D. Andricopulo and Albérico B. F. Da Silva

Molecules 2013, 18(5), 5032-5050; https://doi.org/10.3390/molecules18055032 - 29 Apr 2013

Cited by 11 | Viewed by 5939

Abstract

Quantitative structure–activity relationship (QSAR) studies were performed in order to identify molecular features responsible for the antileishmanial activity of 61 adenosine analogues acting as inhibitors of the enzyme glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). Density functional theory (DFT) was employed [...] Read more.

Quantitative structure–activity relationship (QSAR) studies were performed in order to identify molecular features responsible for the antileishmanial activity of 61 adenosine analogues acting as inhibitors of the enzyme glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). Density functional theory (DFT) was employed to calculate quantum-chemical descriptors, while several structural descriptors were generated with Dragon 5.4. Variable selection was undertaken with the ordered predictor selection (OPS) algorithm, which provided a set with the most relevant descriptors to perform PLS, PCR and MLR regressions. Reliable and predictive models were obtained, as attested by their high correlation coefficients, as well as the agreement between predicted and experimental values for an external test set. Additional validation procedures were carried out, demonstrating that robust models were developed, providing helpful tools for the optimization of the antileishmanial activity of adenosine compounds. Full article

(This article belongs to the Special Issue QSAR and Its Applications)

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238 KiB

Open AccessArticle

Sesquiterpenoids from the Herb of Leonurus japonicus

by Liang Xiong, Qin-Mei Zhou, Cheng Peng, Xiao-Fang Xie, Li Guo, Xiao-Hong Li, Juan Liu, Zhao-Hua Liu and Ou Dai

Molecules 2013, 18(5), 5051-5058; https://doi.org/10.3390/molecules18055051 - 29 Apr 2013

Cited by 38 | Viewed by 6563

Abstract

Two new sesquiterpenoids, (−)-(1S*,2S*,3R*)-3-ethoxycupar-5-ene-1,2-diol (1) and (−)-(1S*,4S*,9S*)-1,9-epoxybisabola-2,10-diene-4-ol (2), along with six known compounds 3−8, were isolated from the EtOH extract of the herb of [...] Read more.

Two new sesquiterpenoids, (−)-(1S*,2S*,3R*)-3-ethoxycupar-5-ene-1,2-diol (1) and (−)-(1S*,4S*,9S*)-1,9-epoxybisabola-2,10-diene-4-ol (2), along with six known compounds 3−8, were isolated from the EtOH extract of the herb of Leonurus japonicus. Their structures were elucidated by physical and spectroscopic analysis. In the in vitro assays, compounds 7 and 8 showed obvious antibacterial activity against several bacteria strains, while compound 3 significantly inhibited abnormal increase of platelet aggregation induced by ADP. Full article

(This article belongs to the Section Natural Products Chemistry)

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369 KiB

Open AccessArticle

Novel Substituted Heteroaromatic Piperazine and Piperidine Derivatives as Inhibitors of Human Enterovirus 71 and Coxsackievirus A16

by Xian Zhang, Hongliang Wang, Yuhuan Li, Ruiyuan Cao, Wu Zhong, Zhibing Zheng, Gang Wang, Junhai Xiao and Song Li

Molecules 2013, 18(5), 5059-5071; https://doi.org/10.3390/molecules18055059 - 29 Apr 2013

Cited by 11 | Viewed by 5892

Abstract

A series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein VP1. The preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against EV71 and Coxsackievirus A16 [...] Read more.

A series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein VP1. The preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against EV71 and Coxsackievirus A16 with low cytotoxicity. Full article

(This article belongs to the Section Medicinal Chemistry)

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650 KiB

Open AccessArticle

Characterisation of Phenolic Compounds in South African Plum Fruits (Prunus salicina Lindl.) using HPLC Coupled with Diode-Array, Fluorescence, Mass Spectrometry and On-Line Antioxidant Detection

by Alet Venter, Elizabeth Joubert and Dalene De Beer

Molecules 2013, 18(5), 5072-5090; https://doi.org/10.3390/molecules18055072 - 2 May 2013

Cited by 36 | Viewed by 8427

Abstract

Phenolic compounds are abundant secondary metabolites in plums, with potential health benefits believed to be due to their antioxidant activity, amongst others. Phenolic characterisation of South African Prunus salicina Lindl. plums is necessary to fully evaluate their potential health benefits. An HPLC method [...] Read more.

Phenolic compounds are abundant secondary metabolites in plums, with potential health benefits believed to be due to their antioxidant activity, amongst others. Phenolic characterisation of South African Prunus salicina Lindl. plums is necessary to fully evaluate their potential health benefits. An HPLC method using diode-array detection (DAD) for quantification of phenolic compounds was improved and fluorescence detection (FLD) was added for quantification of flavan-3-ols. Validation of the HPLC-DAD-FLD method showed its suitability for quantification of 18 phenolic compounds, including flavan-3-ols using FLD, and phenolic acids, anthocyanins and flavonols using DAD. The method was suitable for characterisation of the phenolic composition of 11 South African plum cultivars and selections, including various types with yellow and red skin and flesh. The method was used in conjunction with mass spectrometry (MS) to identify 24 phenolic compounds. Neochlorogenic acid and cyanidin-3-O-glucoside were the major compounds in most of the plums, while cyanidin-3-O-glucoside was absent in Sun Breeze plums with yellow skin and flesh. Post-column on-line coupling of the ABTS^•+ scavenging assay with HPLC-DAD enabled qualitative evaluation of the relative contribution of individual phenolic compounds to the antioxidant activity. The flavan-3-ols, neochlorogenic acid and cyanidin-3-O-glucoside displayed the largest antioxidant response peaks. Full article

(This article belongs to the Special Issue Phytochemicals: Analytical and Medicinal Chemistry)

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713 KiB

Open AccessArticle

C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation

by Andrijana Meščić, Svjetlana Krištafor, Ivana Novaković, Amar Osmanović, Ursina Müller, Davorka Završnik, Simon M. Ametamey, Leonardo Scapozza and Silvana Raić-Malić

Molecules 2013, 18(5), 5104-5124; https://doi.org/10.3390/molecules18055104 - 2 May 2013

Cited by 7 | Viewed by 6110

Abstract

The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields [...] Read more.

The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent. Full article

(This article belongs to the Section Medicinal Chemistry)

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355 KiB

Open AccessArticle

A Facile Synthesis of Functionalized Dispirooxindole Derivatives via a Three-Component 1,3-Dipolar Cycloaddition Reaction

by Jun He, Guang Ouyang, Zhixiang Yuan, Rongsheng Tong, Jianyou Shi and Liang Ouyang

Molecules 2013, 18(5), 5142-5154; https://doi.org/10.3390/molecules18055142 - 3 May 2013

Cited by 27 | Viewed by 6632

Abstract

An efficient synthesis of novel dispirooxindoles has been achieved through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and an α-amino acid with the dipolarophile 5-benzylideneimidazolidine-2,4-dione. The improved procedure features mild reaction conditions, high yields, [...] Read more.

An efficient synthesis of novel dispirooxindoles has been achieved through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and an α-amino acid with the dipolarophile 5-benzylideneimidazolidine-2,4-dione. The improved procedure features mild reaction conditions, high yields, high diastereoselectivities, a one-pot procedure and operational simplicity. Full article

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677 KiB

Open AccessArticle

Understanding Acid Lability of Cysteine Protecting Groups

by Iván Ramos-Tomillero, Lorena Mendive-Tapia, Miriam Góngora-Benítez, Ernesto Nicolás, Judit Tulla-Puche and Fernando Albericio

Molecules 2013, 18(5), 5155-5162; https://doi.org/10.3390/molecules18055155 - 6 May 2013

Cited by 15 | Viewed by 6658

Abstract

Cys-disulfide bonds contribute to the stabilization of peptide and protein structures. The synthesis of these molecules requires a proper protection of Cys residues, which is crucial to prevent side-reactions and also to achieve the correct Cys connectivity. Here we undertook a mechanistic study [...] Read more.

Cys-disulfide bonds contribute to the stabilization of peptide and protein structures. The synthesis of these molecules requires a proper protection of Cys residues, which is crucial to prevent side-reactions and also to achieve the correct Cys connectivity. Here we undertook a mechanistic study of a set of well-known acid-labile Cys protecting groups, as well other new promising groups, in order to better understand the nature of their acid-lability. The stability of the carbocation generated during the acid treatment was found to have a direct impact on the removal of the protective groups from the corresponding protected Cys-containing peptides. Hence a combination of steric and conjugative effects determines the stability of the carbocations generated. Here we propose diphenylmethyl (Dpm) as a promising protecting group on the basis of its intermediate relative carbocation stability. All the optimized geometries and energies presented in this study were determined using a B3LYP/6-31G(d,p) calculation. The results discussed herein may be of broader applicability for the development of new protecting groups. Full article

(This article belongs to the Special Issue Disulfide and Diselenide Chemistry)

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522 KiB

Open AccessArticle

Retention of Halogenated Solutes on Stationary Phases Containing Heavy Atoms

by Toshio Miwa, Atsushi Yamamoto, Mitsuru Saito and Yoshinori Inoue

Molecules 2013, 18(5), 5163-5171; https://doi.org/10.3390/molecules18055163 - 6 May 2013

Cited by 5 | Viewed by 4338

Abstract

To examine the effects of weak intermolecular interactions on solid-phase extraction (SPE) and chromatographic separation, we synthesized some novel stationary phases with a heavy atom effect layer by immobilizing halogenated aromatic rings and hydroxyl groups onto the surface of a hydrophilic base polymer. [...] Read more.

To examine the effects of weak intermolecular interactions on solid-phase extraction (SPE) and chromatographic separation, we synthesized some novel stationary phases with a heavy atom effect layer by immobilizing halogenated aromatic rings and hydroxyl groups onto the surface of a hydrophilic base polymer. Using SPE cartridges packed with the functionalized materials, we found that the heavy atom stationary phases could selectively retain halophenols in organic solvents, such as 1-propanol which blocks the hydrogen bonding, or acetonitrile which blocks the p-p interaction. The extraction efficiency of the materials toward the halophenols depended on the dipole moments of phenoxy groups present as functional groups. On the other hand, the extraction efficiency of solutes toward the functional group depended on their molar refractions, i.e., induced dipole moments. The retention of the solutes to the stationary phase ultimately depended on not only strong intermolecular interactions, but also the effects of weak interactions such as the dispersion force. Full article

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404 KiB

Open AccessArticle

A-Type Proanthocyanidins from the Stems of Ephedra sinica (Ephedraceae) and Their Antimicrobial Activities

by Xinyu Zang, Mingying Shang, Feng Xu, Jing Liang, Xuan Wang, Masayuki Mikage and Shaoqing Cai

Molecules 2013, 18(5), 5172-5189; https://doi.org/10.3390/molecules18055172 - 6 May 2013

Cited by 61 | Viewed by 8522

Abstract

Phytochemical investigation of the n-BuOH-soluble fraction of the EtOH extract of the herbaceous stems of Ephedra sinica, which is known as Ephedrae Herba in Traditional Chinese Medicine, led to the isolation and identification of 12 A-type proanthocyanidins, containing five dimers, two [...] Read more.

Phytochemical investigation of the n-BuOH-soluble fraction of the EtOH extract of the herbaceous stems of Ephedra sinica, which is known as Ephedrae Herba in Traditional Chinese Medicine, led to the isolation and identification of 12 A-type proanthocyanidins, containing five dimers, two trimers and five tetramers [i.e., (+)-epigallocatechin-(2α→O→7,4α→8)-(-)-catechin, named ephedrannin D₁, a dimer; epigallocatechin-(2α→O→7,4α→8)-epigallocatechin-(4α→8)-catechin (ephedrannin Tr₁), a trimer; and epigallocatechin-(2α→O→7,4α→8)-epigallocatechin-(4α→8)-epigallocatechin-(2α→O→7,4α→8)-gallocatechin, named ephedrannin Te₁, a tetramer). Tetramers composed of gallocatechin are reported for the first time in Ephedraceae. Catechin, epicatechin, gallocatechin, epigallocatechin and four known dimers were also isolated. The structures were elucidated by extensive spectroscopic analysis. The absolute configurations of the 4α linkages, which were confirmed by NOESY and CD experiments, are the outstanding characteristic of most of these isolated A-type proanthocyanidins. The antimicrobial activities of these compounds were tested by measuring the minimum inhibitory concentrations (MIC) against bacteria (both Gram positive and Gram negative) and fungi, and were found to be in the range of 0.00515–1.38 mM. Compounds 6, 8, 10 and 11 exhibited moderate antimicrobial activities against Canidia albicans. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

The Short-Term Effects of Soybean Intake on Oxidative and Carbonyl Stress in Men and Women

by Peter Celec, Július Hodosy, Roland Pálffy, Roman Gardlík, Lukáč Halčák and Daniela Ostatníková

Molecules 2013, 18(5), 5190-5200; https://doi.org/10.3390/molecules18055190 - 7 May 2013

Cited by 15 | Viewed by 5804

Abstract

Beyond other beneficial effects, a soy-rich diet has been shown to reduce the risk of cardiovascular diseases and diabetic complications. Reduction of oxidative and carbonyl stress has been proposed as the underlying mechanism, but the evidence for this is lacking. The aim of [...] Read more.

Beyond other beneficial effects, a soy-rich diet has been shown to reduce the risk of cardiovascular diseases and diabetic complications. Reduction of oxidative and carbonyl stress has been proposed as the underlying mechanism, but the evidence for this is lacking. The aim of our study was to evaluate the effects of short-term increased soy intake on oxidative and carbonyl stress parameters in young volunteers. Young healthy probands (omnivores) of both genders (55 women, 33 men) were given soybeans (2 g/kg bodyweight daily) for one week. Markers of oxidative and carbonyl stress were measured in plasma at the beginning and at the end of one week soybean intake and after another week of a wash-out period. Total antioxidant capacity was increased by soybean intake in both genders. This led to decreased levels of advanced oxidation protein products in women, but not in men. On the contrary, in men, soybean intake increased lipoperoxidation. No effects on carbonyl stress markers (advanced glycation end products-specific fluorescence and fructosamine) were found. Soybean intake has gender-specific effects on oxidative stress in young healthy probands potentially due to divergent action and metabolism of phytoestrogens in men and women. Effects of soybean intake on carbonyl stress should be evaluated in longer studies. Full article

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Open AccessArticle

A Facile Asymmetric Synthesis of (S)-14-Methyl-1-Octadecene, the Sex Pheromone of the Peach Leafminer Moth

by Tao Zhang, Wei-Li Ma, Tian-Rui Li, Jia Wu, Jun-Run Wang and Zhen-Ting Du

Molecules 2013, 18(5), 5201-5208; https://doi.org/10.3390/molecules18055201 - 7 May 2013

Cited by 14 | Viewed by 6360

Abstract

An asymmetric synthesis of 14-methyl-1-octadecene, the sex pheromone of the peach leafminer moth has been achieved. The target molecule was synthesized in six linear steps and in 30.3% overall yield from commercially available hexanoyl chloride, (S)-4-benzyloxazolidin-2-one and 1,9-nonanediol. The hexanoyl chloride [...] Read more.

An asymmetric synthesis of 14-methyl-1-octadecene, the sex pheromone of the peach leafminer moth has been achieved. The target molecule was synthesized in six linear steps and in 30.3% overall yield from commercially available hexanoyl chloride, (S)-4-benzyloxazolidin-2-one and 1,9-nonanediol. The hexanoyl chloride was connected with (S)-4-benzyloxazolidin-2-one, and with the induction of the chiral oxazolidinone auxiliary, after chiral methylation, LAH reduction and then tosylation gave the chiral key intermediate 5 in high stereoselectivity. 1,9-Nonanediol, was selectively brominated, THP protected and subjected to Li₂CuCl₄-mediated C-C coupling to afford a C₁₂ intermediate. The target molecule, (S)-14-methyl-1-octadecene, was obtained after the two parts were subjected to a second Li₂CuCl₄-mediated C-C coupling. Our synthetic approach represents the first time a substrate-control asymmetric synthesis of (S)-14-methyl-1-octadecene has been reported. Full article

(This article belongs to the Section Organic Chemistry)

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Theoretical Study of H/D Isotope Effects on Nuclear Magnetic Shieldings Using an ab initio Multi-Component Molecular Orbital Method

by Taro Udagawa, Takayoshi Ishimoto and Masanori Tachikawa

Molecules 2013, 18(5), 5209-5220; https://doi.org/10.3390/molecules18055209 - 7 May 2013

Cited by 17 | Viewed by 5505

Abstract

We have theoretically analyzed the nuclear quantum effect on the nuclear magnetic shieldings for the intramolecular hydrogen-bonded systems of σ-hydroxy acyl aromatic species using the gauge-including atomic orbital technique combined with our multi-component density functional theory. The effect of H/D quantum nature for [...] Read more.

We have theoretically analyzed the nuclear quantum effect on the nuclear magnetic shieldings for the intramolecular hydrogen-bonded systems of σ-hydroxy acyl aromatic species using the gauge-including atomic orbital technique combined with our multi-component density functional theory. The effect of H/D quantum nature for geometry and nuclear magnetic shielding changes are analyzed. Our study clearly demonstrated that the geometrical changes of hydrogen-bonds induced by H/D isotope effect (called geometrical isotope effect: GIE) is the dominant factor of deuterium isotope effect on ¹³C chemical shift. Full article

(This article belongs to the Collection Isotope Effects)

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Changes in SeMSC, Glucosinolates and Sulforaphane Levels, and in Proteome Profile in Broccoli (Brassica oleracea var. Italica) Fertilized with Sodium Selenate

by Ignacio Sepúlveda, Herna Barrientos, Andrea Mahn and Alejandra Moenne

Molecules 2013, 18(5), 5221-5234; https://doi.org/10.3390/molecules18055221 - 7 May 2013

Cited by 19 | Viewed by 6747

Abstract

The aim of this work was to analyze the effect of sodium selenate fortification on the content of selenomethyl selenocysteine (SeMSC), total glucosinolates and sulforaphane, as well as the changes in protein profile of the inflorescences of broccoli (Brassica oleracea var. Italica [...] Read more.

The aim of this work was to analyze the effect of sodium selenate fortification on the content of selenomethyl selenocysteine (SeMSC), total glucosinolates and sulforaphane, as well as the changes in protein profile of the inflorescences of broccoli (Brassica oleracea var. Italica). Two experimental groups were considered: plants treated with 100 mmol/L sodium selenate (final concentration in the pot) and control plants treated with water. Fortification began 2 weeks after transplantation and was repeated once a week during 10 weeks. Broccoli florets were harvested when they reached appropriate size. SeMSC content in broccoli florets increased significantly with sodium selenate fortification; but total glucosinolates and sulforaphane content as well as myrosinase activity were not affected. The protein profile of broccoli florets changed due to fortification with sodium selenate. Some proteins involved in general stress-responses were up-regulated, whereas down-regulated proteins were identified as proteins involved in protection against pathogens. This is the first attempt to evaluate the physiological effect of fortification with sodium selenate on broccoli at protein level. The results of this work will contribute to better understanding the metabolic processes related with selenium uptake and accumulation in broccoli. Full article

(This article belongs to the Special Issue Selenium and Tellurium Chemistry)

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Simultaneous Determination of Structurally Diverse Compounds in Different Fangchi Species by UHPLC-DAD and UHPLC-ESI-MS/MS

by Hee-Jung Sim, Ji Hee Kim, Kang Ro Lee and Jongki Hong

Molecules 2013, 18(5), 5235-5250; https://doi.org/10.3390/molecules18055235 - 7 May 2013

Cited by 34 | Viewed by 7193

Abstract

Two bisbenzylisoquinoline alkaloids, two morphine alkaloids, one aporphine alkaloid, syringaresinol and aristolochic acid І were selected as marker compounds and simultaneously analyzed using an ultra-high pressure liquid chromatography-diode array detection (UHPLC-DAD) method. These marker compounds were used for the quality control of Fangchi [...] Read more.

Two bisbenzylisoquinoline alkaloids, two morphine alkaloids, one aporphine alkaloid, syringaresinol and aristolochic acid І were selected as marker compounds and simultaneously analyzed using an ultra-high pressure liquid chromatography-diode array detection (UHPLC-DAD) method. These marker compounds were used for the quality control of Fangchi species of different origins, including Sinomenium acutum, Stephania tetrandra, Cocculus trilobus and Aristolochia fangchi. A reversed-phase UHPLC-DAD method was developed and validated for the simultaneous quantification of structurally diverse markers in different Fangchi species. In addition, an UHPLC-electrospray ionization tandem mass spectrometry (ESI-MS/MS) method was used for marker identification in Fangchi species, which provided diagnostic MS/MS spectral patterns that were dependent upon the marker structures. The UHPLC-MS/MS data were used to confirm and complement the UHPLC-DAD quality evaluation results. Additionally, magnoflorine and syringaresinol were observed for the first time in S. tetrandra and C. trilobus, respectively. Twenty different Fangchi species samples were analyzed for aristolochic acid I, syringaresinol and the alkaloids using the UHPLC-DAD and MS/MS method. Based on the levels of markers and principal component analysis (PCA), this method allowed for the clear classification of the samples into four different groups representing samples originating from the four species. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and Biological Activity of 6-Selenocaffeine: Potential Modulator of Chemotherapeutic Drugs in Breast Cancer Cells

by Inês L. Martins, Joana P. Miranda, Nuno G. Oliveira, Ana S. Fernandes, Sandrina Gonçalves and Alexandra M. M. Antunes

Molecules 2013, 18(5), 5251-5264; https://doi.org/10.3390/molecules18055251 - 8 May 2013

Cited by 26 | Viewed by 7563

Abstract

We report the development of a new microwave-based synthetic methodology mediated by Woollins’ reagent that allowed an efficient conversion of caffeine into 6-selenocaffeine. A preliminary evaluation on the modulation of antioxidant activity upon selenation of caffeine, using the DPPH assay, indicated a mild [...] Read more.

We report the development of a new microwave-based synthetic methodology mediated by Woollins’ reagent that allowed an efficient conversion of caffeine into 6-selenocaffeine. A preliminary evaluation on the modulation of antioxidant activity upon selenation of caffeine, using the DPPH assay, indicated a mild antioxidant activity for 6-selenocaffeine, contrasting with caffeine, that exhibited no antioxidant activity under the same experimental conditions. Interestingly, whereas 6-selenocaffeine has revealed to have a low cytotoxic potential in both MCF10A and MCF-7 breast cells (24 h, up to 100 µM, MTT assay), a differential effect was observed when used in combination with the anticancer agents doxorubicin and oxaliplatin in MCF-7 breast cancer cells. The co-treatment of doxorubicin (1 µM) and 6-selenocaffeine (100 µM) resulted in a slight decrease in cellular viability when compared to doxorubicin (1 µM) alone. Conversely, the seleno-caffeine derivative at the same concentration markedly increased the viability of oxaliplatin (100 µM)-treated cells (p < 0.01). Overall, this work highlights an emerging methodology to synthesize organoselenium compounds and points out the differential roles of 6-selenocaffeine in the modulation of the cytotoxicity of anticancer agents. Full article

(This article belongs to the Special Issue Selenium and Tellurium Chemistry)

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Chemical Constituents from the Rhizomes of Smilax glabra and Their Antimicrobial Activity

by Shuo Xu, Ming-Ying Shang, Guang-Xue Liu, Feng Xu, Xuan Wang, Cheng-Chao Shou and Shao-Qing Cai

Molecules 2013, 18(5), 5265-5287; https://doi.org/10.3390/molecules18055265 - 8 May 2013

Cited by 111 | Viewed by 16706

Abstract

Six new phenolic compounds, named smiglabrone A (1), smiglabrone B (2), smilachromanone (3), smiglastilbene (4), smiglactone (5), smiglabrol (6), together with fifty-seven known ones 7–63 were isolated [...] Read more.

Six new phenolic compounds, named smiglabrone A (1), smiglabrone B (2), smilachromanone (3), smiglastilbene (4), smiglactone (5), smiglabrol (6), together with fifty-seven known ones 7–63 were isolated from the rhizomes of Smilax glabra. Their structures were elucidated on the basis of extensive spectroscopic analyses, as well as by comparison with literature data. Twenty-seven of these compounds were obtained from and identified in the genus Smilax for the first time. The absolute configuration of (2S)-1,2-O-di-trans-p-coumaroylglycerol (43) was determined for the first time using the exciton-coupled circular dichroism (ECCD) method. Thirty isolated compounds were evaluated for their antimicrobial activity against three Gram-negative bacteria, three Gram-positive bacteria and one fungus, and the corresponding structure-activity relationships were also discussed. Eighteen compounds were found to be antimicrobial against the microorganisms tested and the minimum inhibitory concentrations (MIC) were in the range of 0.0794–3.09 mM. Among them, compound 1 showed antimicrobial activity against Canidia albicans with MIC value of 0.146 mM, which was stronger than cinchonain Ia with an MIC of 0.332 mM. Compounds 3 and 4 exhibited inhibitory activity against Staphylococcus aureus with MIC values of 0.303 and 0.205 mM, respectively. The results indicated that these antimicrobial constituents of this crude drug might be responsible for its clinical antimicrobial effect. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Chitosan Based Heterogeneous Catalyses: Chitosan-Grafted-Poly(4-Vinylpyridne) as an Efficient Catalyst for Michael Additions and Alkylpyridazinyl Carbonitrile Oxidation

by Khaled D. Khalil and Hamad M. Al-Matar

Molecules 2013, 18(5), 5288-5305; https://doi.org/10.3390/molecules18055288 - 8 May 2013

Cited by 41 | Viewed by 9376

Abstract

Chitosan-grafted-poly(4-vinylpyridine) (Cs-PVP) copolymers could be synthesized under heterogeneous conditions in presence of a potassium persulfate and sodium sulfite redox system. The synthesized graft copolymer could be utilized effectively, in the form of beads, as an efficient catalyst for Michael additions of active methylenes [...] Read more.

Chitosan-grafted-poly(4-vinylpyridine) (Cs-PVP) copolymers could be synthesized under heterogeneous conditions in presence of a potassium persulfate and sodium sulfite redox system. The synthesized graft copolymer could be utilized effectively, in the form of beads, as an efficient catalyst for Michael additions of active methylenes to functionally substituted alkenes. Moreover, methyl moiety oxidation in methyl pyridazinyl carbonitriles by H₂O₂ in the presence of chitosan-g-polyvinyl pyridine–supported iron (III) complex, Cs-PVP/Fe, could be affected. A variety of pyrans, naphthopyrans, and thiopyrans could be synthesized efficiently in the presence of these graft copolymer beads by novel catalytic routes. These polymeric catalysts could be used instead of the old toxic commercial organic basic catalysts, piperidine or pyridine, and could be readily isolated from the reaction mixture and recycled several times without significant loss of catalytic activity. Full article

(This article belongs to the Special Issue Organocatalysis)

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Isolation of Nematicidal Triterpenoid Saponins from Pulsatilla koreana Root and Their Activities against Meloidogyne incognita

by Wei Li, Ya Nan Sun, Xi Tao Yan, Seo Young Yang, Suk Jun Lee, Hyo Jeung Byun, Chang Sup Moon, Byung Soo Han and Young Ho Kim

Molecules 2013, 18(5), 5306-5316; https://doi.org/10.3390/molecules18055306 - 8 May 2013

Cited by 27 | Viewed by 7042

Abstract

Pulsatilla koreana, a species endemic to Korea, is an important herb used in traditional medicine to treat amoebic dysentery and malaria. In the present study, 23 oleanane-type triterpenoid saponins 1–23 and eight lupane-type triterpenoid saponins 24–31 were isolated [...] Read more.

Pulsatilla koreana, a species endemic to Korea, is an important herb used in traditional medicine to treat amoebic dysentery and malaria. In the present study, 23 oleanane-type triterpenoid saponins 1–23 and eight lupane-type triterpenoid saponins 24–31 were isolated from the roots of P. koreana. Their structures were elucidated on the basis of spectroscopic data. The methanol extract and isolated compounds were next assessed for nematicidal activity against the root-knot nematode (Meloidogyne incognita). The methanol extract showed strong nematicidal activity after 48 h, with a LC₅₀ value of 92.8 μg/mL. Compounds 2, 5, 9, 20, and 21 showed significant effects, with LC₅₀ values ranging from 70.1 to 94.7 μg/mL after 48 h. These results suggest that triterpenoid saponins from P. koreana should be explored as potential natural nematicides for developing new agents to control root-knot nematode disease Full article

(This article belongs to the Section Natural Products Chemistry)

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Characterization of Volatile Components in Makgeolli, a Traditional Korean Rice Wine, with or without Pasteurization, During Storage

by Hye-Jung Park, Sang Mi Lee, Sang Hoon Song and Young-Suk Kim

Molecules 2013, 18(5), 5317-5325; https://doi.org/10.3390/molecules18055317 - 8 May 2013

Cited by 50 | Viewed by 8477

Abstract

Changes in the volatile components of unpasteurized and pasteurized makgeolli during 30 days of storage were investigated by gas chromatography-mass spectrometry (GC-MS) and GC-olfactometry (GC-O). A total of 11 odor-active compounds such as 3-methyl-1-butanol (isoamyl alcohol), 2-methyl-1-butanol, 2,3-butanediol, butanoic acid, 3-methylbutanoic acid (isovaleric [...] Read more.

Changes in the volatile components of unpasteurized and pasteurized makgeolli during 30 days of storage were investigated by gas chromatography-mass spectrometry (GC-MS) and GC-olfactometry (GC-O). A total of 11 odor-active compounds such as 3-methyl-1-butanol (isoamyl alcohol), 2-methyl-1-butanol, 2,3-butanediol, butanoic acid, 3-methylbutanoic acid (isovaleric acid), 2-methylbutanoic acid, 3-(methylthio)-1-propanol (methionol), 2-phenylethanol, ethyl decanoate, ethyl dodecanoate, and ethyl tetradecanoate were determined in both the pasteurized and unpasteurized makgeolli during 30 days of storage. Although there were no significant differences in the concentrations of odor-active compounds at the initial storage time, most of odor-active compounds were more significantly increased in unpasteurized makgeolli compared to the pasteurized one during the storage period. Full article

(This article belongs to the Special Issue Flavors and Fragrances)

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Characterization of Phenolic Constituents from Ephedra Herb Extract

by Yoshiaki Amakura, Morio Yoshimura, Saori Yamakami, Takashi Yoshida, Daigo Wakana, Masashi Hyuga, Sumiko Hyuga, Toshihiko Hanawa and Yukihiro Goda

Molecules 2013, 18(5), 5326-5334; https://doi.org/10.3390/molecules18055326 - 10 May 2013

Cited by 46 | Viewed by 9049

Abstract

Nine known compounds: trans-cinnamic acid, catechin, syringin, epicatechin, symplocoside, kaempferol 3-O-rhamnoside 7-O-glucoside, isovitexin 2-O-rhamnoside, herbacetin 7-O-glucoside, and pollenitin B and a new flavonoid glycoside, characterized as herbacetin 7-O-neohesperidoside (1) on [...] Read more.

Nine known compounds: trans-cinnamic acid, catechin, syringin, epicatechin, symplocoside, kaempferol 3-O-rhamnoside 7-O-glucoside, isovitexin 2-O-rhamnoside, herbacetin 7-O-glucoside, and pollenitin B and a new flavonoid glycoside, characterized as herbacetin 7-O-neohesperidoside (1) on the basis of spectroscopic analysis and chemical evidence, were isolated from a traditional crude drug, “Ephedra herb extract”. Compound 1 had no effects on HGF-induced motility, whereas herbacetin, which is an aglycone of 1, significantly inhibited it. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Chelator-Accelerated One-Pot ‘Click’ Labeling of Small Molecule Tracers with 2-[¹⁸F]Fluoroethyl Azide

by Eva Galante, Bent Wilhelm Schoultz, Matthias Koepp and Erik Årstad

Molecules 2013, 18(5), 5335-5347; https://doi.org/10.3390/molecules18055335 - 10 May 2013

Cited by 14 | Viewed by 6391

Abstract

2-[¹⁸F]Fluoroethyl azide ([¹⁸F]FEA) can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [¹⁸F]fluoride (half-life 110 min), and has become widely used as a reagent for ‘click’ labeling of PET tracers. However, distillation of [¹⁸F]FEA [...] Read more.

2-[¹⁸F]Fluoroethyl azide ([¹⁸F]FEA) can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [¹⁸F]fluoride (half-life 110 min), and has become widely used as a reagent for ‘click’ labeling of PET tracers. However, distillation of [¹⁸F]FEA is typically required, which is time-consuming and unpractical for routine applications. In addition, copper(I)-catalyzed cycloaddition of [¹⁸F]FEA with non-activated alkynes, and with substrates containing labile functional groups, can be challenging. Herein, we report a highly efficient and practical ligand-accelerated one-pot/two-step method for ‘click’ labeling of small molecule tracers with [¹⁸F]FEA. The method exploits the ability of the copper(I) ligand bathophenanthrolinedisulfonate to accelerate the rate of the cycloaddition reaction. As a result, alkynes can be added directly to the crude reaction mixture containing [¹⁸F]FEA, and as cyclisation occurs almost immediately at room temperature, the reaction is tolerant to labile functional groups. The method was demonstrated by reacting [¹⁸F]FEA with a series of alkyne-functionalized 6-halopurines to give the corresponding triazoles in 55–76% analytical radiochemical yield. Full article

(This article belongs to the Special Issue PET Chemistry in Molecular Imaging)

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Diterpenylhydroquinones from Natural ent-Labdanes Induce Apoptosis through Decreased Mitochondrial Membrane Potential

by Joan Villena, Alejandro Madrid, Iván Montenegro, Enrique Werner, Mauricio Cuellar and Luis Espinoza

Molecules 2013, 18(5), 5348-5359; https://doi.org/10.3390/molecules18055348 - 10 May 2013

Cited by 13 | Viewed by 4568

Abstract

In this study, we examined the cytotoxic effects of seven ent-labdane derivatives 1–7 (0–100 μM) in different human cancer cell lines. Our results showed that compounds 1–3 exhibited significant dose-dependent inhibition on the growth of the three different [...] Read more.

In this study, we examined the cytotoxic effects of seven ent-labdane derivatives 1–7 (0–100 μM) in different human cancer cell lines. Our results showed that compounds 1–3 exhibited significant dose-dependent inhibition on the growth of the three different human cell lines, according to the sulphorhodamine B assay and produced morphological changes consistent with apoptosis, as confirmed by Hoestch 3342 staining analysis. They induced apoptosis in various cancer cell lines, as shown by nuclear condensation and fragmentation and caspase 3 activation. Such induction was associated with the depletion of mitochondrial membrane potential. These activities led to the cleavage of caspases and the trigger of cell death process. Overall, the compounds showed potent proapoptotic effects on the two different cancer cell lines, suggesting that the compounds deserve more extensive investigation of their potential medicinal applications. Full article

(This article belongs to the Section Medicinal Chemistry)

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Oxidative Debromination and Degradation of Tetrabromo-bisphenol A by a Functionalized Silica-Supported Iron(III)-tetrakis(p-sulfonatophenyl)porphyrin Catalyst

by Qianqian Zhu, Yusuke Mizutani, Shohei Maeno and Masami Fukushima

Molecules 2013, 18(5), 5360-5372; https://doi.org/10.3390/molecules18055360 - 10 May 2013

Cited by 18 | Viewed by 6378

Abstract

Tetrabromobisphenol A (TBBPA), a commonly used brominated flame retardant, also functions as an endocrine disruptor. Thus, the degradation of TBBPA has attracted considerable interest among the scientific community. Iron(III)-porphyrin complexes are generally regarded as “green” catalysts and have been reported to catalyze the [...] Read more.

Tetrabromobisphenol A (TBBPA), a commonly used brominated flame retardant, also functions as an endocrine disruptor. Thus, the degradation of TBBPA has attracted considerable interest among the scientific community. Iron(III)-porphyrin complexes are generally regarded as “green” catalysts and have been reported to catalyze the efficient degradation and dehalogenation of halogenated phenols in environmental wastewaters. However, they are quickly deactivated due to self-degradation in the presence of an oxygen donor, such as KHSO₅. In the present study, an iron(III)-tetrakis (p-sulfonatophenyl)-porphyrin (FeTPPS) was immobilized on imidazole-modified silica (FeTPPS/IPS) via coordination of the Fe(III) with the nitrogen atom in imidazole to suppress self-degradation and thus enhance the catalyst reusability. The oxidative degradation and debromination of TBBPA and the influence of humic acid (HA), a major component in leachates, on the oxidation of TBBPA was investigated. More than 95% of the TBBPA was degraded in the pH range from 3 to 8 in the absence of HA, while the optimal pH for the reaction was at pH 8 in the presence of HA. Although the rate of degradation was decreased in the presence of HA, over 95% of the TBBPA was degraded within 12 h in the presence of 28 mg-C L⁻¹ of HA. At pH 8, the FeTPPS/IPS catalyst could be reused up to 10 times without any detectable loss of activity for TBBPA for degradation and debromination, even in the presence of HA. Full article

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Curcumin and Its Carbocyclic Analogs: Structure-Activity in Relation to Antioxidant and Selected Biological Properties

by Khushwant S. Bhullar, Amitabh Jha, Dani Youssef and H. P. Vasantha Rupasinghe

Molecules 2013, 18(5), 5389-5404; https://doi.org/10.3390/molecules18055389 - 10 May 2013

Cited by 81 | Viewed by 8654

Abstract

Curcumin is the major phenolic compound present in turmeric (Curcuma longa L.). Curcumin and 15 novel analogs were investigated for their antioxidant and selected biological activities. Strong relationships between the structure and evaluated activity revealed that the compounds with specific functional groups [...] Read more.

Curcumin is the major phenolic compound present in turmeric (Curcuma longa L.). Curcumin and 15 novel analogs were investigated for their antioxidant and selected biological activities. Strong relationships between the structure and evaluated activity revealed that the compounds with specific functional groups and carbon skeleton had specific biological profiles. Among the compounds tested, the derivatives (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e), and (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)-cyclopentanone (3d) and the parent compound curcumin exhibited the strongest free radical scavenging and antioxidant capacity. Concerning the other biological activities studied the compound (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxy-phenyl)-acryloyl)cyclopentanone (3d) was the most potent angiotensin converting enzyme (ACE) inhibitor, while the derivatives (E)-2-(4-hydroxybenzylidene)-6-((E)-3-(4-hydroxyphenyl)acryloyl)cyclohexanone (2b), (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclohexanone (2e) and (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e) exhibited strong tyrosinase inhibition. Moreover, (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)-acryloyl)cyclohexanone (2e) was also found to be the strongest human HIV-1 protease inhibitor in vitro among the tested compounds. Cytotoxicity studies using normal human lung cells revealed that the novel curcumin as well as its carbocyclic analogs are not toxic. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Antagonist Effects of Veratric Acid against UVB-Induced Cell Damages

by Seoung Woo Shin, Eunsun Jung, Seungbeom Kim, Kyung-Eun Lee, Jong-Kyung Youm and Deokhoon Park

Molecules 2013, 18(5), 5405-5419; https://doi.org/10.3390/molecules18055405 - 10 May 2013

Cited by 35 | Viewed by 7678

Abstract

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic [...] Read more.

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid) is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis, Characterization and Activity Evaluation of Matrinic Acid Derivatives as Potential Antiproliferative Agents

by Fan Chao, Dong-En Wang, Rui Liu, Qin Tu, Jian-Jun Liu and Jinyi Wang

Molecules 2013, 18(5), 5420-5433; https://doi.org/10.3390/molecules18055420 - 10 May 2013

Cited by 17 | Viewed by 5960

Abstract

A series of new matrinic acid derivatives 5a–e was synthesized. The chemical structures of the synthesized compounds were confirmed by ¹H-NMR, ¹³C-NMR, and electrospray ionization mass spectroscopy. The anti-tumor activities were also investigated in vitro by evaluating the effect [...] Read more.

A series of new matrinic acid derivatives 5a–e was synthesized. The chemical structures of the synthesized compounds were confirmed by ¹H-NMR, ¹³C-NMR, and electrospray ionization mass spectroscopy. The anti-tumor activities were also investigated in vitro by evaluating the effect of synthesized compounds on the proliferation of A375, A549, HeLa, and HepG2 cells. Compound 5e was found to be the most potent against A375 and HeLa cells, with IC₅₀ values of 37 and 75.5 μg/mL, respectively. Compounds 5b, 5c, 5g, and 5h also exhibited antiproliferative activities against A549 cells, with IC₅₀ values within the 36.2–47 μg/mL range. For HepG2 cells, 5e and 5i, with IC₅₀ values of 78.9 and 61 μg/mL, respectively, showed higher antiproliferative activity than taxol. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Optimization and Characterization of Chitosan Films for Transdermal Delivery of Ondansetron

by Aslı Sedef Can, Meryem Sedef Erdal, Sevgi Güngör and Yıldız Özsoy

Molecules 2013, 18(5), 5455-5471; https://doi.org/10.3390/molecules18055455 - 10 May 2013

Cited by 76 | Viewed by 8279

Abstract

The aim of this study was to develop novel transdermal films of ondansetron HCl with high molecular weight chitosan as matrix polymer and 2-(2-ethoxy-ethoxy) ethanol (Transcutol^®) as plasticizer. In this context, firstly the physicochemical properties of gels used to formulate transdermal [...] Read more.

The aim of this study was to develop novel transdermal films of ondansetron HCl with high molecular weight chitosan as matrix polymer and 2-(2-ethoxy-ethoxy) ethanol (Transcutol^®) as plasticizer. In this context, firstly the physicochemical properties of gels used to formulate transdermal films were characterized and, physicochemical properties and bioadhesiveness of the transdermal films prepared with chitosan gels were assessed. The impact of three different types of terpenes, namely limonene, nerolidol and eucalyptol on in vitro skin permeation of ondansetron from transdermal films were also examined. ATR-FTIR measurements were performed to investigate the effects of the chitosan film formulations on in vitro conformational order of stratum corneum intercellular lipids after 24 h permeation study. The results showed that the chitosan gels consisting of Transcutol^® as plasticizer and terpenes as penetration enhancer may be used to prepare transdermal films of ondansetron due to the good mechanical properties and bioadhesiveness of the transdermal films. Eucalyptol (1%) showed higher permeation enhancer effect than the other terpenes and control. ATR-FTIR data confirmed that finding in which eucalyptol induced a blue shift in the both CH2 asymmetric and symmetric absorbance peak positions indicating increased lipid fluidity of stratum corneum. Full article

(This article belongs to the Special Issue Chitins and Chitosans)

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Open AccessArticle

Enantioselective Esterification of Ibuprofen under Microwave Irradiation

by Zecheng Yang, Xuedun Niu, Xuedong Fang, Ge Chen, Hong Zhang, Hong Yue, Lei Wang, Dantong Zhao and Zhi Wang

Molecules 2013, 18(5), 5472-5481; https://doi.org/10.3390/molecules18055472 - 13 May 2013

Cited by 9 | Viewed by 5390

Abstract

Enantioselective esterification of ibuprofen has been successfully carried out in an organic solvent catalyzed by recombinant APE 1547 (a thermophilic esterase from the archaeon Aeropyrum pernix K1). Here we used microwave irradiation (MW) as the mode of heating to improve the enzyme performance. [...] Read more.

Enantioselective esterification of ibuprofen has been successfully carried out in an organic solvent catalyzed by recombinant APE 1547 (a thermophilic esterase from the archaeon Aeropyrum pernix K1). Here we used microwave irradiation (MW) as the mode of heating to improve the enzyme performance. Under the optimum conditions, the enzyme activity of APE 1547 was 4.16 μmol/mg/h and the enantioselectivity (E value) was 52.9. Compared with conventional heating, the enzyme activity and the enantioselectivity were increased about 21.9-fold and 1.4-fold, respectively. The results also indicated that APE 1547 can maintain 95% of its activity even after being used five times, suggesting that the enzyme is stable under low power MW conditions. Full article

(This article belongs to the Section Organic Chemistry)

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Synthesis, Antifungal and Antitumor Activity of Novel (Z)-5-Hetarylmethylidene-1,3-thiazol-4-ones and (Z)-5-Ethylidene-1,3-thiazol-4-ones

by Alberto Insuasty, Juan Ramírez, Marcela Raimondi, Carlos Echeverry, Jairo Quiroga, Rodrigo Abonia, Manuel Nogueras, Justo Cobo, María Victoria Rodríguez, Susana A. Zacchino and Braulio Insuasty

Molecules 2013, 18(5), 5482-5497; https://doi.org/10.3390/molecules18055482 - 13 May 2013

Cited by 21 | Viewed by 5699

Abstract

New hetaryl- and alkylidenerhodanine derivatives 3a–d, 3e, and 4a–d were prepared from heterocyclic aldehydes 1a–d or acetaldehyde 1e. The treatment of several rhodanine derivatives 3a–d and 3e with piperidine or morpholine in [...] Read more.

New hetaryl- and alkylidenerhodanine derivatives 3a–d, 3e, and 4a–d were prepared from heterocyclic aldehydes 1a–d or acetaldehyde 1e. The treatment of several rhodanine derivatives 3a–d and 3e with piperidine or morpholine in THF under reflux, afforded (Z)-5-(hetarylmethylidene)-2-(piperidin-1-yl)thiazol-4(5H)-ones and 2-morpholinothiazol-4(5H)-ones 5a–d, 6a–d, and (Z)-5-ethylidene-2-morpholinothiazol-4(5H)-one (5e), respectively, in good yields. Structures of all compounds were determined by IR, 1D and 2D NMR and mass spectrometry. Several of these compounds were screened by the U.S. National Cancer Institute (NCI) to assess their antitumor activity against 60 different human tumor cell lines. Compound 3c showed high activity against HOP-92 (Non-Small Cell Lung Cancer), which was the most sensitive cell line, with GI₅₀ = 0.62 μM and LC₅₀ > 100 μM from the in vitro assays. In vitro antifungal activity of these compounds was also determined against 10 fungal strains. Compound 3e showed activity against all fungal strains tested, but showed high activity against Saccharomyces cerevisiae (MIC 3.9 μg/mL). Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Synthesis and Biological Evaluation of 3-Benzisoxazolyl-4-indolylmaleimides as Potent, Selective Inhibitors of Glycogen Synthase Kinase-3β

by Qing Ye, Meng Li, Yubo Zhou, Tao Pang, Lei Xu, Jiayi Cao, Liang Han, Yujin Li, Weisi Wang, Jianrong Gao and Jia Li

Molecules 2013, 18(5), 5498-5516; https://doi.org/10.3390/molecules18055498 - 13 May 2013

Cited by 17 | Viewed by 6881

Abstract

A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC₅₀ value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships [...] Read more.

A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC₅₀ value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ring and N¹-position of the indole ring had varying degrees of influence on the GSK-3β inhibitory potency. Compounds 7c, 7f, 7j–l and 7o–q could obviously reduce Aβ-induced Tau hyperphosphorylation by inhibiting GSK-3β in a cell-based functional assay. Full article

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Synthesis of a New ent-Cyclozonarone Angular Analog, and Comparison of Its Cytotoxicity and Apoptotic Effects with ent-Cyclozonarone

by Natalia Quiñones Sobarzo, Iván Montenegro Venegas, Cristian Salas Sánchez, Luis Espinoza Catalán, Cristóbal Carrasco Rojas, Valentina Ulloa Valdivia, Joan Villena García and Mauricio Cuellar Fritis

Molecules 2013, 18(5), 5517-5530; https://doi.org/10.3390/molecules18055517 - 13 May 2013

Cited by 3 | Viewed by 4813

Abstract

The synthesis of a newangular analog 11 of cyclozonarone was achieved via Diels-Alder reaction between a sesquiterpene-1,3-diene and 1,4-benzoquinone. The cytotoxic activity of ent-cyclozonarone [(+)-10] and the angular (−)-cyclozonarone analog 11 has been determined in three human cancer cell lines [...] Read more.

The synthesis of a newangular analog 11 of cyclozonarone was achieved via Diels-Alder reaction between a sesquiterpene-1,3-diene and 1,4-benzoquinone. The cytotoxic activity of ent-cyclozonarone [(+)-10] and the angular (−)-cyclozonarone analog 11 has been determined in three human cancer cell lines and in normal fibroblasts using the sulforhodamine B assay. The analyzed isomers induce cell death in different cancer cell lines by eliciting nuclear condensation and fragmentation, decreasing mitochondrial membrane permeability and increasing caspase-3 activity, all traits indicating apoptosis, with the effects of (+)-10 being stronger than those of 11 in all cases. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Water Extractable Arabinoxylan Aerogels Prepared by Supercritical CO₂ Drying

by Jorge Marquez-Escalante, Elizabeth Carvajal-Millan, Mario Miki-Yoshida, Lorena Alvarez-Contreras, Alma Rosa Toledo-Guillén, Jaime Lizardi-Mendoza and Agustín Rascón-Chu

Molecules 2013, 18(5), 5531-5542; https://doi.org/10.3390/molecules18055531 - 14 May 2013

Cited by 24 | Viewed by 5895

Abstract

Water extractable arabinoxylan (WEAX) aerogels were prepared by extracting the solvent from the alcogels (WEAX hydrogels with an alcohol as the solvent) with carbon dioxide under supercritical conditions. WEAX aerogels were characterized using scanning electron microscopy and adsorption and desorption nitrogen isotherms. The [...] Read more.

Water extractable arabinoxylan (WEAX) aerogels were prepared by extracting the solvent from the alcogels (WEAX hydrogels with an alcohol as the solvent) with carbon dioxide under supercritical conditions. WEAX aerogels were characterized using scanning electron microscopy and adsorption and desorption nitrogen isotherms. The micrographs indicate a heterogeneous porous network structure in WEAX aerogel. Adsorption/desorption nitrogen isotherms of this material were type IV, which confirm that this material possess a mesoporous structure. WEAX aerogels rehydration capability was evaluated and the water absorption mechanism was determined. The WEAX aerogels water absorption mechanism was non-Fickian (n = 0.54). Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Three New Multiflorane-Type Triterpenes from Pumpkin (Cucurbita maxima) Seeds

by Takashi Kikuchi, Mika Takebayashi, Mayumi Shinto, Takeshi Yamada and Reiko Tanaka

Molecules 2013, 18(5), 5568-5579; https://doi.org/10.3390/molecules18055568 - 14 May 2013

Cited by 14 | Viewed by 5329

Abstract

Three new multiflorane-type triterpenes; 7a-methoxymultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (1), 7-oxomultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (2), and multiflora-7,9(11)-diene-3a,29-diol 3-p-hydroxybenzoate-29-benzoate (3), were isolated from seeds of Cucurbita maxima, along with three known compounds. Compound 3 and multiflora-7,9(11)-diene-3a-29-diol 3-benzoate (5) [...] Read more.

Three new multiflorane-type triterpenes; 7a-methoxymultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (1), 7-oxomultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (2), and multiflora-7,9(11)-diene-3a,29-diol 3-p-hydroxybenzoate-29-benzoate (3), were isolated from seeds of Cucurbita maxima, along with three known compounds. Compound 3 and multiflora-7,9(11)-diene-3a-29-diol 3-benzoate (5) exhibited potent inhibitory effects on melanogenesis, with low cytotoxicities, and 2 exhibited single-digit micromolar cytotoxicity against HL-60 and P388 cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Hexachlorocyclotriphosphazene (HCCP)-Mediated Direct Formation of Thioethers and Ethers from Quinazolin-4(3H)-ones

by Baoxiang Hu, Xiaochu Zhang, Lili Sheng, Ming Guo, Zhenlu Shen, Xinquan Hu, Nan Sun and Weimin Mo

Molecules 2013, 18(5), 5580-5593; https://doi.org/10.3390/molecules18055580 - 15 May 2013

Cited by 7 | Viewed by 6400

Abstract

A hexachlorocyclotriphosphazene (HCCP)-mediated direct formation of quinazoline (thio)ethers from quinazolin-4(3H)-ones has been developed. Treatment of quinazolin-4(3H)-ones with HCCP, diisopropylethylamine (DIPEA), and thiophenols resulted in formation of the corresponding 4-arylthioquinazoline derivatives in moderate to excellent yields. This method has also [...] Read more.

A hexachlorocyclotriphosphazene (HCCP)-mediated direct formation of quinazoline (thio)ethers from quinazolin-4(3H)-ones has been developed. Treatment of quinazolin-4(3H)-ones with HCCP, diisopropylethylamine (DIPEA), and thiophenols resulted in formation of the corresponding 4-arylthioquinazoline derivatives in moderate to excellent yields. This method has also been utilized to prepare 4-aryloxyquinazoline and 4-alkoxyquinazoline derivatives using phenols and sodium alkoxides as the nucleophiles. Full article

(This article belongs to the Section Organic Chemistry)

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Development of a New Positron Emission Tomography Tracer for Targeting Tumor Angiogenesis: Synthesis, Small Animal Imaging, and Radiation Dosimetry

by Cam Patterson, C. Brandon Frederick, Hong Yuan, Laura A. Dyer, Pamela Lockyer, David S. Lalush and Anka N. Veleva

Molecules 2013, 18(5), 5594-5610; https://doi.org/10.3390/molecules18055594 - 15 May 2013

Cited by 8 | Viewed by 6553

Abstract

Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of [...] Read more.

Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with ⁶⁴Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET). To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with ⁶⁴Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c.) Lewis lung carcinoma (LLC) mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide. Full article

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Photophysical Studies of a New Water Soluble Indocarbocyanine Dye Adsorbed onto Microcrystalline Cellulose and beta-Cyclodextrin

by Reda M. El-Shishtawy, Anabela S. Oliveira, Paulo Almeida, Diana P. Ferreira, David S. Conceição and Luis F. Vieira Ferreira

Molecules 2013, 18(5), 5648-5668; https://doi.org/10.3390/molecules18055648 - 15 May 2013

Cited by 7 | Viewed by 7340

Abstract

A water-soluble indocarbocyanine dye was synthesized and its photophysics were studied for the first time on two solid hosts, microcrystalline cellulose and b-cyclodextrin, as well as in homogeneous media. The inclusion of the indocarbocyanine moiety onto microcrystalline cellulose increased the dye aggregation with [...] Read more.

A water-soluble indocarbocyanine dye was synthesized and its photophysics were studied for the first time on two solid hosts, microcrystalline cellulose and b-cyclodextrin, as well as in homogeneous media. The inclusion of the indocarbocyanine moiety onto microcrystalline cellulose increased the dye aggregation with both H and J aggregates being formed. Adsorption on b-cyclodextrin enhanced aggregation in a similar way. The fluorescence quantum yields were determined for the powdered samples of the cyanine dye on the two hosts and a significant increase was observed relative to homogeneous solution. A remarkable concentration dependence was also detected in both cases. A lifetime distribution analysis has shown that the indocarbocyanine dye mainly occupies the amorphous part of cellulose and is not entrapped in the crystalline part of this host. In the b-CD case, the adsorption occurs outside the host cavity. In both hosts a strong concentration quenching effect is observed and only monomers emit. Both adsorptions may be explained by stereochemical constraints imposed by the two long sulphoethyl tails linked to nitrogen atoms of the indocarbocyanine dye. Full article

(This article belongs to the Special Issue New Trends in Photochemistry)

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Effects of Chirality on the Antifungal Potency of Methylated Succinimides Obtained by Aspergillus fumigatus Biotransformations. Comparison with Racemic Ones

by Maximiliano Sortino, Agustina Postigo and Susana Zacchino

Molecules 2013, 18(5), 5669-5683; https://doi.org/10.3390/molecules18055669 - 15 May 2013

Cited by 15 | Viewed by 5416

Abstract

Eighteen (3R) and (3R,4R)-N-phenyl-, N-phenylalkyl and N-arylsuccinimides were prepared with high enantioselectivity by biotransformation of maleimides with A. fumigatus. This environmentally friendly, clean and economical procedure was performed by the whole-cell fungal [...] Read more.

Eighteen (3R) and (3R,4R)-N-phenyl-, N-phenylalkyl and N-arylsuccinimides were prepared with high enantioselectivity by biotransformation of maleimides with A. fumigatus. This environmentally friendly, clean and economical procedure was performed by the whole-cell fungal bioconversion methodology. Their corresponding eighteen racemic succinimides were prepared instead by synthetic methods. Both, the racemic and the chiral succinimides were tested simultaneously by the microbroth dilution method of CLSI against a panel of human opportunistic pathogenic fungi of clinical importance. Chiral succinimides showed higher antifungal activity than the corresponding racemic ones and the differences in activity were established by statistical methods. The bottlenecks for developing chiral drugs are how to obtain them through a low-cost procedure and with high enantiomeric excess. Results presented here accomplish both these objectives, opening an avenue for the development of asymmetric succinimides as new antifungal drugs for pharmaceutical use. Full article

(This article belongs to the Section Molecular Diversity)

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Identification of Insecticidal Constituents of the Essential Oil of Acorus calamus Rhizomes against Liposcelis bostrychophila Badonnel

by Xin Chao Liu, Li Gang Zhou, Zhi Long Liu and Shu Shan Du

Molecules 2013, 18(5), 5684-5696; https://doi.org/10.3390/molecules18055684 - 15 May 2013

Cited by 91 | Viewed by 9225

Abstract

The aim of this research was to determine the chemical composition of the essential oil of Acorus calamus rhizomes, its insecticidal activity against the booklouse, (Liposcelis bostrychophila) and to isolate any insecticidal constituents from the essential oil. The essential oil of [...] Read more.

The aim of this research was to determine the chemical composition of the essential oil of Acorus calamus rhizomes, its insecticidal activity against the booklouse, (Liposcelis bostrychophila) and to isolate any insecticidal constituents from the essential oil. The essential oil of A. calamus rhizomes was obtained by hydrodistillation and analyzed by GC-FID and GC-MS. A total of 32 components of the essential oil of A. calamus rhizomes was identified and the principal compounds in the essential oil were determined to be α-asarone (50.09%), (E)-methylisoeugenol (14.01%), and methyleugenol (8.59%), followed by β-asarone (3.51%), α-cedrene (3.09%) and camphor (2.42%). Based on bioactivity-guided fractionation, the three active constituents were isolated from the essential oil and identified as methyleugenol, (E)-methylisoeugenol and α-asarone. The essential oil exhibited contact toxicity against L. bostrychophila with an LD₅₀ value of 100.21 µg/cm² while three constituent compounds, α-asarone, methyleugenol, and (E)-methylisoeugenol had LD₅₀ values of 125.73 µg/cm², 103.22 µg/cm² and 55.32 µg/cm², respectively. Methyleugenol and (E)-methylisoeugenol possessed fumigant toxicity against L. bostrychophila adults with LC₅₀ values of 92.21 μg/L air and 143.43 μg/L air, respectively, while the crude essential oil showed an LC₅₀ value of 392.13 μg/L air. The results indicate that the essential oil of A. calamus rhizomes and its constituent compounds have potential for development into natural fumigants/insecticides for control of the booklice. Full article

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A Novel Multi-Component Reaction to Imidazo[4,5-g]-quinazolines

by Li Li, Qianqian Zhang, Bo Liu and Gang Liu

Molecules 2013, 18(5), 5697-5705; https://doi.org/10.3390/molecules18055697 - 16 May 2013

Cited by 1 | Viewed by 5532

Abstract

The trace impurities discovered after extended storage of a 5-amino- benzimidazole library were determined as imidazo[4,5-g]quinazoline derivatives by extensive spectroscopic data analysis. The formation of this highly aromatic heterocyclic ring involved a novel multi-component reaction, using which several novel compounds were prepared. Its [...] Read more.

The trace impurities discovered after extended storage of a 5-amino- benzimidazole library were determined as imidazo[4,5-g]quinazoline derivatives by extensive spectroscopic data analysis. The formation of this highly aromatic heterocyclic ring involved a novel multi-component reaction, using which several novel compounds were prepared. Its mechanism was deduced as a cascade of chemical transformations, including the formation of a Schiff’s base, intramolecular hetero-Diels-Alder reaction, defluorination and dehydrogenation. Full article

(This article belongs to the Section Organic Chemistry)

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Virtual Screening and Structure-Based Discovery of Indole Acylguanidines as Potent β-secretase (BACE1) Inhibitors

by Yiquan Zou, Li Li, Wuyan Chen, Tiantian Chen, Lanping Ma, Xin Wang, Bing Xiong, Yechun Xu and Jingkang Shen

Molecules 2013, 18(5), 5706-5722; https://doi.org/10.3390/molecules18055706 - 16 May 2013

Cited by 24 | Viewed by 7960

Abstract

Proteolytic cleavage of amyloid precursor protein by β-secretase (BACE1) is a key step in generating the N-terminal of β-amyloid (Aβ), which further forms into amyloid plaques that are considered as the hallmark of Alzheimer’s disease. Inhibitors of BACE1 can reduce the levels [...] Read more.

Proteolytic cleavage of amyloid precursor protein by β-secretase (BACE1) is a key step in generating the N-terminal of β-amyloid (Aβ), which further forms into amyloid plaques that are considered as the hallmark of Alzheimer’s disease. Inhibitors of BACE1 can reduce the levels of Aβ and thus have a therapeutic potential for treating the disease. We report here the identification of a series of small molecules bearing an indole acylguanidine core structure as potent BACE1 inhibitors. The initial weak fragment was discovered by virtual screening, and followed with a hit-to-lead optimization. With the aid of co-crystal structures of two discovered inhibitors (compounds 19 and 25) with BACE1, we explored the SAR around the indole and aryl groups, and obtained several BACE1 inhibitors about 1,000-fold more potent than the initial fragment hit. Accompanying the lead optimization, a previously under-explored sub-site opposite the flap loop was redefined as a potential binding site for later BACE1 inhibitor design. Full article

(This article belongs to the Section Medicinal Chemistry)

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Four New Citrinin Derivatives from a Marine-Derived Penicillium sp. Fungal Strain

by Mei Ling Wang, Chun Hua Lu, Qing Yan Xu, Si Yang Song, Zhi Yu Hu and Zhong Hui Zheng

Molecules 2013, 18(5), 5723-5735; https://doi.org/10.3390/molecules18055723 - 16 May 2013

Cited by 49 | Viewed by 7474

Abstract

Four new citrinin derivatives, including two citrinin dimers and two citrinin monomer derivatives, were isolated and identified from a marine-derived fungal strain Penicillium sp. ML226 along with six known related compounds. Their structures were elucidated by spectroscopic and chemical methods. The new compounds [...] Read more.

Four new citrinin derivatives, including two citrinin dimers and two citrinin monomer derivatives, were isolated and identified from a marine-derived fungal strain Penicillium sp. ML226 along with six known related compounds. Their structures were elucidated by spectroscopic and chemical methods. The new compounds showed modest cytotoxic activity against HepG-2 cell line and weak antimicrobial activity against Staphylococcus aureus. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Production of Flavours and Fragrances via Bioreduction of (4R)-(-)-Carvone and (1R)-(-)-Myrtenal by Non-Conventional Yeast Whole-Cells

by Marta Goretti, Benedetta Turchetti, Maria Rita Cramarossa, Luca Forti and Pietro Buzzini

Molecules 2013, 18(5), 5736-5748; https://doi.org/10.3390/molecules18055736 - 16 May 2013

Cited by 29 | Viewed by 8272

Abstract

As part of a program aiming at the selection of yeast strains which might be of interest as sources of natural flavours and fragrances, the bioreduction of (4R)-(−)-carvone and (1R)-(−)-myrtenal by whole-cells of non-conventional yeasts (NCYs) belonging to the [...] Read more.

As part of a program aiming at the selection of yeast strains which might be of interest as sources of natural flavours and fragrances, the bioreduction of (4R)-(−)-carvone and (1R)-(−)-myrtenal by whole-cells of non-conventional yeasts (NCYs) belonging to the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Kazachstania, Kluyveromyces, Lindnera, Nakaseomyces, Vanderwaltozyma and Wickerhamomyces was studied. Volatiles produced were sampled by means of headspace solid-phase microextraction (SPME) and the compounds were analysed and identified by gas chromatography–mass spectroscopy (GC-MS). Yields (expressed as % of biotransformation) varied in dependence of the strain. The reduction of both (4R)-(−)-carvone and (1R)-(−)-myrtenal were catalyzed by some ene-reductases (ERs) and/or carbonyl reductases (CRs), which determined the formation of (1R,4R)-dihydrocarvone and (1R)-myrtenol respectively, as main flavouring products. The potential of NCYs as novel whole-cell biocatalysts for selective biotransformation of electron-poor alkenes for producing flavours and fragrances of industrial interest is discussed. Full article

(This article belongs to the Special Issue Flavors and Fragrances)

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Open AccessArticle

Synthesis and Characterization of Oil-Chitosan Composite Spheres

by Keng-Shiang Huang, Chih-Yu Wang, Chih-Hui Yang, Alexandru Mihai Grumezescu, Yung-Sheng Lin, Chao-Pin Kung, I-Yin Lin, Yi-Ching Chang, Wei-Jie Weng and Wei-Ting Wang

Molecules 2013, 18(5), 5749-5760; https://doi.org/10.3390/molecules18055749 - 16 May 2013

Cited by 16 | Viewed by 7717

Abstract

Oil-chitosan composite spheres were synthesized by encapsulation of sunflower seed oil in chitosan droplets, dropping into NaOH solution and in situ solidification. Hydrophilic materials (i.e., iron oxide nanoparticles) and lipophilic materials (i.e., rhodamine B or epirubicin) could be encapsulated [...] Read more.

Oil-chitosan composite spheres were synthesized by encapsulation of sunflower seed oil in chitosan droplets, dropping into NaOH solution and in situ solidification. Hydrophilic materials (i.e., iron oxide nanoparticles) and lipophilic materials (i.e., rhodamine B or epirubicin) could be encapsulated simultaneously in the spheres in a one step process. The diameters of the prepared spheres were 2.48 ± 0.11 mm (pure chitosan spheres), 2.31 ± 0.08 mm (oil-chitosan composites), 1.49 ± 0.15 mm (iron-oxide embedded oil-chitosan composites), and 1.69 ± 0.1 mm (epirubicin and iron oxide encapsulated oil-chitosan composites), respectively. Due to their superparamagnetic properties, the iron-oxide embedded oil-chitosan composites could be guided by a magnet. A lipophilic drug (epirubicin) could be loaded in the spheres with encapsulation rate measured to be 72.25%. The lipophilic fluorescent dye rhodamine B was also loadable in the spheres with red fluorescence being observed under a fluorescence microscope. We have developed a novel approach to an in situ process for fabricating oil-chitosan composite spheres with dual encapsulation properties, which are potential multifunctional drug carriers. Full article

(This article belongs to the Special Issue Chitins and Chitosans)

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Open AccessArticle

Anti-Infective Potential of Marine Invertebrates and Seaweeds from the Brazilian Coast

by Éverson Miguel Bianco, Simone Quintana De Oliveira, Caroline Rigotto, Maiko Luis Tonini, Tatiana Da Rosa Guimarães, Francine Bittencourt, Lidiane Pires Gouvêa, Cassandra Aresi, Maria Tereza Rojo De Almeida, Maria Izabel Goularte Moritz, Cintia Dalcuche Leal Martins, Fernando Scherner, João Luís Carraro, Paulo Antunes Horta, Flávio Henrique Reginatto, Mario Steindel, Cláudia Maria Oliveira Simões and Eloir Paulo Schenkel

Molecules 2013, 18(5), 5761-5778; https://doi.org/10.3390/molecules18055761 - 16 May 2013

Cited by 41 | Viewed by 7754

Abstract

This manuscript describes the evaluation of anti-infective potential in vitro of organic extracts from nine sponges, one ascidian, two octocorals, one bryozoan, and 27 seaweed species collected along the Brazilian coast. Antimicrobial activity was tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC [...] Read more.

This manuscript describes the evaluation of anti-infective potential in vitro of organic extracts from nine sponges, one ascidian, two octocorals, one bryozoan, and 27 seaweed species collected along the Brazilian coast. Antimicrobial activity was tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231) by the disk diffusion method. Antiprotozoal activity was evaluated against Leishmania braziliensis (MHOM/BR/96/LSC96-H3) promastigotes and Trypanosoma cruzi (MHOM/BR/00/Y) epimastigotes by MTT assay. Activity against intracellular amastigotes of T. cruzi and L. brasiliensis in murine macrophages was also evaluated. Antiviral activity was tested against Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the plaque number reduction assay (IC₅₀). Cytotoxicity on VERO cells was evaluated by the MTT assay (CC₅₀). The results were expressed as SI = CC₅₀/IC₅₀. The most promising antimicrobial results were obtained against S. aureus and C. albicans with Dragmacidon reticulatum. Among the seaweeds, only Osmundaria obtusiloba showed moderate activity against P. aeruginosa. Concerning antiprotozoal activity, Bugula neritina, Carijoa riseii, Dragmaxia anomala and Haliclona (Halichoclona) sp. showed the most interesting results, mainly against extracellular promastigote forms of L. braziliensis (66, 35.9, 97.2, and 43.6% inhibition, respectively). Moreover, six species of seaweeds Anadyomene saldanhae, Caulerpa cupressoides, Canistrocarpus cervicornis, Dictyota sp., Ochtodes secundiramea, and Padina sp. showed promising results against L. braziliensis (87.9, 51.7, 85.9, 93.3, 99.7, and 80.9% inhibition, respectively), and only Dictyota sp. was effective against T. cruzi (60.4% inhibition). Finally, the antiherpes activity was also evaluated, with Haliclona (Halichoclona) sp. and Petromica citrina showing the best results (SI = 11.9 and SI > 5, respectively). All the active extracts deserve special attention in further studies to chemically characterize the bioactive compounds, and to perform more refined biological assays. Full article

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Open AccessArticle

Effects of Polysaccharides from Different Species of Dendrobium (Shihu) on Macrophage Function

by Lan-Zhen Meng, Guang-Ping Lv, De-Jun Hu, Kit-Leong Cheong, Jing Xie, Jing Zhao and Shao-Ping Li

Molecules 2013, 18(5), 5779-5791; https://doi.org/10.3390/molecules18055779 - 17 May 2013

Cited by 71 | Viewed by 8778

Abstract

Dendrobium spp. are precious medicinal plants, used in China for thousands of years as health foods and nutrients. Polysaccharides are the main effective ingredients in Dendrobium plants. In this study, the chemical characteristics and the effects of crude polysaccharides (CPs) from five species [...] Read more.

Dendrobium spp. are precious medicinal plants, used in China for thousands of years as health foods and nutrients. Polysaccharides are the main effective ingredients in Dendrobium plants. In this study, the chemical characteristics and the effects of crude polysaccharides (CPs) from five species of Dendrobium on macrophage function were investigated and compared in vitro for the first time. Chemical characteristic studies showed that CPs from different species of Dendrobium were diverse, displaying widely varied Mw distributions and molar ratios of monosaccharides. Their effects on macrophage functions, such as promoting phagocytosis, release of NO and cytokines IL-1α, IL-6, IL-10 and TNF-α, were also different. Moreover, CPs from D. officinale, especially collected from Yunnan Province, exerted the strongest immunomodulatory activities and could be explored as a novel potential functional food. The diverse chemical characteristics of CPs from different species of Dendrobium might contribute to their varied effects on macrophage functions, which should be further investigated. Full article

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Open AccessArticle

Effect of Leguminous Lectins on the Growth of Rhizobium tropici CIAT899

by Mayron Alves De Vasconcelos, Cláudio Oliveira Cunha, Francisco Vassiliepe Sousa Arruda, Victor Alves Carneiro, Rafaela Mesquita Bastos, Fábio Martins Mercante, Kyria Santiago do Nascimento, Benildo Sousa Cavada, Ricardo Pires dos Santos and Edson Holanda Teixeira

Molecules 2013, 18(5), 5792-5803; https://doi.org/10.3390/molecules18055792 - 17 May 2013

Cited by 5 | Viewed by 5432

Abstract

Rhizobium tropici is a Gram-negative bacterium that induces nodules and fixed atmospheric nitrogen in symbiotic association with Phaseolus vulgaris (common bean) and some other leguminous species. Lectins are proteins that specifically bind to carbohydrates and, consequently, modulate different biological functions. In this study, [...] Read more.

Rhizobium tropici is a Gram-negative bacterium that induces nodules and fixed atmospheric nitrogen in symbiotic association with Phaseolus vulgaris (common bean) and some other leguminous species. Lectins are proteins that specifically bind to carbohydrates and, consequently, modulate different biological functions. In this study, the d-glucose/ d-mannose-binding lectins (from seeds of Dioclea megacarpa, D. rostrata and D. violacea) and D-galactose-binding lectins (from seeds of Bauhinia variegata, Erythina velutina and Vatairea macrocarpa) were purified using chromatographic techniques and evaluated for their effect on the growth of R. tropici CIAT899. All lectins were assayed with a satisfactory degree of purity according to SDS-PAGE analysis, and stimulated bacterial growth; in particular, the Dioclea rostrata lectin was the most active among all tested proteins. As confirmed in the present study, both d-galactose- and d-glucose/d-mannose-binding lectins purified from the seeds of leguminous plants may be powerful biotechnological tools to stimulate the growth of R. tropici CIAT99, thus improving symbiotic interaction between rhizobia and common bean and, hence, the production of this field crop. Full article

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Open AccessCommunication

Dried Root of Rehmannia glutinosa Prevents Bone Loss in Ovariectomized Rats

by Dong Wook Lim and Yun Tai Kim

Molecules 2013, 18(5), 5804-5813; https://doi.org/10.3390/molecules18055804 - 17 May 2013

Cited by 53 | Viewed by 8530

Abstract

Dried root of Rehmannia glutinosa is a kidney-tonifying herbal medicine with a long history of safe use in traditional folk medicine for the treatment of joint diseases. This study was conducted to investigate prevention of bone loss by a standardized dried root of [...] Read more.

Dried root of Rehmannia glutinosa is a kidney-tonifying herbal medicine with a long history of safe use in traditional folk medicine for the treatment of joint diseases. This study was conducted to investigate prevention of bone loss by a standardized dried root of R. glutinosa in an ovariectomized (OVX) rat model of osteoporosis. The OVX groups were divided into five groups treated with distilled water, 17β-estradiol (E2 10 µg/kg, once daily, i.p) and dried root of R. glutinosa extracts (DRGE 30, 100, and 300 mg/kg, twice daily, p.o) for eight weeks. We measured the body, organs, and uterus weights, and femur and lumbar vertebrae bone mineral density (BMD), serum alkaline phosphatase (ALP), estradiol levels. The treatments with DRGE 300 mg/kg significantly inhibited BMD decrease in the femur and lumbar (17.5% and 16.4%, p < 0.05, respectively) by OVX without affecting the body, organs, and uterus weights. Also, serum ALP level in the DRGE 300 mg/kg treated group was significantly decreased, but the estradiol level did not change in serum of the DRGE 300 mg/kg treated group. These results show that DRGE is able to prevent OVX-induced bone loss without influencing hormones such as estrogen. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Dimeric Labdane Diterpenes: Synthesis and Antiproliferative Effects

by Mariano Walter Pertino, Cristina Theoduloz, Marco Bastías and Guillermo Schmeda-Hirschmann

Molecules 2013, 18(5), 5936-5953; https://doi.org/10.3390/molecules18055936 - 21 May 2013

Cited by 17 | Viewed by 7170

Abstract

Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been carried out on naturally occurring diterpenes and semisynthetic derivatives, but much less is known on the effects of diterpene dimers. The [...] Read more.

Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been carried out on naturally occurring diterpenes and semisynthetic derivatives, but much less is known on the effects of diterpene dimers. The aim of the present work was to synthesize dimeric diterpenes from the labdane imbricatolic acid using esters, ethers and the triazole ring as linkers. Some 18 new derivatives were prepared and the compounds were evaluated for antiproliferative activity on human normal fibroblasts (MRC-5) and the following human tumor cell lines: AGS, SK-MES-1, J82 and HL-60. The diethers 8–10, differing in the number of CH2 units in the linker, presented better antiproliferative activity with a maximum effect for the derivative 9. The best antiproliferative effect against HL-60 cells was found for compounds 3 and 17, with IC50 values of 22.3 and 23.2 μM, lower than that found for the reference compound etoposide (2.23 μM). The compounds 9, 17 and 11 were the most active derivatives towards AGS cells with IC50 values of 17.8, 23.4 and 26.1 μM. A free carboxylic acid function seems relevant for the effect as several of the compounds showed less antiproliferative effect after methylation. Full article

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Open AccessArticle

Green Biosynthesis and Characterization of Magnetic Iron Oxide (Fe₃O₄) Nanoparticles Using Seaweed (Sargassum muticum) Aqueous Extract

by Mahnaz Mahdavi, Farideh Namvar, Mansor Bin Ahmad and Rosfarizan Mohamad

Molecules 2013, 18(5), 5954-5964; https://doi.org/10.3390/molecules18055954 - 21 May 2013

Cited by 537 | Viewed by 22678

Abstract

The synthesis of nanoparticles has become a matter of great interest in recent times due to their various advantageous properties and applications in a variety of fields. The exploitation of different plant materials for the biosynthesis of nanoparticles is considered a green technology [...] Read more.

The synthesis of nanoparticles has become a matter of great interest in recent times due to their various advantageous properties and applications in a variety of fields. The exploitation of different plant materials for the biosynthesis of nanoparticles is considered a green technology because it does not involve any harmful chemicals. In this study, iron oxide nanoparticles (Fe₃O₄-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (BS, Sargassum muticum) water extract containing sulphated polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. The structural and properties of the Fe₃O₄-NPs were investigated by X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy (FESEM), energy dispersive X-ray fluorescence spectrometry (EDXRF), vibrating sample magnetometry (VSM) and transmission electron microscopy. The average particle diameter as determined by TEM was found to be 18 ± 4 nm. X-ray diffraction showed that the nanoparticles are crystalline in nature, with a cubic shape. The nanoparticles synthesized through this biosynthesis method can potentially useful in various applications. Full article

(This article belongs to the Special Issue Nano-catalysts and Nano-technologies for Green Organic Synthesis)

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Open AccessArticle

Interactive Effect of Salicylic Acid on Some Physiological Features and Antioxidant Enzymes Activity in Ginger (Zingiber officinale Roscoe)

by Ali Ghasemzadeh and Hawa Z. E. Jaafar

Molecules 2013, 18(5), 5965-5979; https://doi.org/10.3390/molecules18055965 - 21 May 2013

Cited by 42 | Viewed by 7563

Abstract

The effect of foliar salicylic acid (SA) applications (10⁻³ and 10⁻⁵ M) on activities of nitrate reductase, guaiacol peroxidase (POD), superoxide dismutases (SOD), catalase (CAT) and proline enzymes and physiological parameters was evaluated in two ginger varieties (Halia Bentong and Halia [...] Read more.

The effect of foliar salicylic acid (SA) applications (10⁻³ and 10⁻⁵ M) on activities of nitrate reductase, guaiacol peroxidase (POD), superoxide dismutases (SOD), catalase (CAT) and proline enzymes and physiological parameters was evaluated in two ginger varieties (Halia Bentong and Halia Bara) under greenhouse conditions. In both varieties, tested treatments generally enhanced photosynthetic rate and total dry weight. Photosynthetic rate increases were generally accompanied by increased or unchanged stomatal conductance levels, although intercellular CO₂ concentrations of treated plants were typically lower than in controls. Lower SA concentrations were generally more effective in enhancing photosynthetic rate and plant growth. Exogenous application of SA increased antioxidant enzyme activities and proline content; the greatest responses were obtained in plants sprayed with 10^–5 M SA, with significant increases observed in CAT (20.1%), POD (45.2%), SOD (44.1%) and proline (43.1%) activities. Increased CAT activity in leaves is naturally expected to increase photosynthetic efficiency and thus net photosynthesis by maintaining a constant CO₂ supply. Our results support the idea that low SA concentrations (10^–5 M) may induce nitrite reductase synthesis by mobilizing intracellular NO³⁻ and can provide protection to nitrite reductase degradation in vivo in the absence of NO^3–. Observed positive correlations among proline, SOD, CAT and POD activities in the studied varieties suggest that increased SOD activity was accompanied by increases in CAT and POD activities because of the high demands of H₂O₂ quenching. Full article

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Open AccessArticle

Synthesis of Micheliolide Derivatives and Their Activities against AML Progenitor Cells

by Wei-Wei Ma, Qian-Qian Shi, Ya-Hui Ding, Jing Long, Quan Zhang and Yue Chen

Molecules 2013, 18(5), 5980-5992; https://doi.org/10.3390/molecules18055980 - 21 May 2013

Cited by 20 | Viewed by 6015

Abstract

Micheliolide (MCL) derivatives with etherification or esterification of the hydroxyl group at the C4 position were synthesized and evaluated for their activities against different acute myelogenous leukemia (AML) cell lines. These derivatives demonstrated comparable activities against AML cell lines HL-60 and doxorubicin resistant [...] Read more.

Micheliolide (MCL) derivatives with etherification or esterification of the hydroxyl group at the C4 position were synthesized and evaluated for their activities against different acute myelogenous leukemia (AML) cell lines. These derivatives demonstrated comparable activities against AML cell lines HL-60 and doxorubicin resistant cell line HL-60/A. As to multi-drug resistant AML progenitor cells KG-1a, MCL and some of its derivatives maintained significant activities, and only 1.1–2.7 fold activity reductions were observed when compared with the activities against HL-60, while doxorubicin showed 20-fold activity reduction. Our study demonstrated that the C4 hydroxyl group of MCL might not only be a suitable position for structural modifications, but also be a starting point for the design of appropriate molecular probes to explore the specific targets in the progenitor cell line KG-1a. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Anionic Calixarene-Capped Silver Nanoparticles Show Species-Dependent Binding to Serum Albumins

by Yannick Tauran, Arnaud Brioude, Beomjoon Kim, Florent Perret and Anthony W. Coleman

Molecules 2013, 18(5), 5993-6007; https://doi.org/10.3390/molecules18055993 - 21 May 2013

Cited by 13 | Viewed by 5735

Abstract

The anionic calixarenes para-sulphonatocalix[4]arene and 1,3-di-Ophosphonatocalix[ 4]arene, have been used to cap silver nanoparticles. The binding of these functional particles with regard to various serum albumins (bovine serum albumin, human serum albumin, porcine serum albumin and sheep serum albumin) has been studied by [...] Read more.

The anionic calixarenes para-sulphonatocalix[4]arene and 1,3-di-Ophosphonatocalix[ 4]arene, have been used to cap silver nanoparticles. The binding of these functional particles with regard to various serum albumins (bovine serum albumin, human serum albumin, porcine serum albumin and sheep serum albumin) has been studied by variable temperature fluorescence spectroscopy. The quenching of the fluorescence of the proteins was shown to vary as a function of the anionic calixarene capping molecule and also as a function of the origin of the serum albumin. It is thus possible to discriminate between the different species. Full article

(This article belongs to the Special Issue Calixarenes and Resorcinarenes)

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Open AccessArticle

Different Analytical Approaches in Assessing Antibacterial Activity and the Purity of Commercial Lysozyme Preparations for Dairy Application

by Milena Brasca, Stefano Morandi, Tiziana Silvetti, Veronica Rosi, Stefano Cattaneo and Luisa Pellegrino

Molecules 2013, 18(5), 6008-6020; https://doi.org/10.3390/molecules18056008 - 21 May 2013

Cited by 28 | Viewed by 8271

Abstract

Hen egg-white lysozyme (LSZ) is currently used in the food industry to limit the proliferation of lactic acid bacteria spoilage in the production of wine and beer, and to inhibit butyric acid fermentation in hard and extra hard cheeses (late blowing) caused by [...] Read more.

Hen egg-white lysozyme (LSZ) is currently used in the food industry to limit the proliferation of lactic acid bacteria spoilage in the production of wine and beer, and to inhibit butyric acid fermentation in hard and extra hard cheeses (late blowing) caused by the outgrowth of clostridial spores. The aim of this work was to evaluate how the enzyme activity in commercial preparations correlates to the enzyme concentration and can be affected by the presence of process-related impurities. Different analytical approaches, including turbidimetric assay, SDS-PAGE and HPLC were used to analyse 17 commercial preparations of LSZ marketed in different countries. The HPLC method adopted by ISO allowed the true LSZ concentration to be determined with accuracy. The turbidimetric assay was the most suitable method to evaluate LSZ activity, whereas SDS-PAGE allowed the presence of other egg proteins, which are potential allergens, to be detected. The analytical results showed that the purity of commercially available enzyme preparations can vary significantly, and evidenced the effectiveness of combining different analytical approaches in this type of control. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

An Efficient Synthesis of Aldohexose-Derived Piperidine Nitrones: Precursors of Piperidine Iminosugars

by Hui Zhao, Wen-Bo Zhao, Jian-She Zhu, Yue-Mei Jia and Chu-Yi Yu

Molecules 2013, 18(5), 6021-6034; https://doi.org/10.3390/molecules18056021 - 21 May 2013

Cited by 5 | Viewed by 5976

Abstract

_D-Glucopyranose-derived and _L-idopyranose-derived piperidine nitrones were synthesized in good overall yields through six-step reaction sequence starting from readily available 2,3,4,6-tetra-O-benzyl-D-glucopyranose. The method is efficient and could be general for the synthesis of aldohexose-derived piperidine nitrones which are precursors of piperidine iminosugars. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Impact of Fruit Piece Structure in Yogurts on the Dynamics of Aroma Release and Sensory Perception

by Joshua Mesurolle, Anne Saint-Eve, Isabelle Déléris and Isabelle Souchon

Molecules 2013, 18(5), 6035-6056; https://doi.org/10.3390/molecules18056035 - 21 May 2013

Cited by 22 | Viewed by 7912

Abstract

The aim of this work was to gain insight into the effect of food formulation on aroma release and perception, both of which playing an important role in food appreciation. The quality and quantity of retronasal aroma released during food consumption affect the [...] Read more.

The aim of this work was to gain insight into the effect of food formulation on aroma release and perception, both of which playing an important role in food appreciation. The quality and quantity of retronasal aroma released during food consumption affect the exposure time of olfactory receptors to aroma stimuli, which can influence nutritional and hedonic characteristics, as well as consumption behaviors. In yogurts, fruit preparation formulation can be a key factor to modulate aroma stimulation. In this context, the impact of size and hardness of fruit pieces in fat-free pear yogurts was studied. Proton Transfer Reaction-Mass Spectrometry (PTR-MS) was used to allow sensitive and on-line monitoring of volatile odorous compound release in the breath during consumption. In parallel, a trained panel used sensory profile and Temporal Dominance of Sensations (TDS) methods to characterize yogurt sensory properties and their dynamic changes during consumption. Results showed that the size of pear pieces had few effects on aroma release and perception of yogurts, whereas fruit hardness significantly influenced them. Despite the fact that yogurts presented short and similar residence times in the mouth, this study showed that fruit preparation could be an interesting formulation factor to enhance exposure time to stimuli and thus modify food consumption behaviors. These results could be taken into account to formulate new products that integrate both nutritional and sensory criteria. Full article

(This article belongs to the Special Issue Flavors and Fragrances)

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Open AccessArticle

Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

by Chao Wang, Hao Zhang, Fengrong Xu, Yan Niu, Yun Wu, Xin Wang, Yihong Peng, Jing Sun, Lei Liang and Ping Xu

Molecules 2013, 18(5), 6057-6091; https://doi.org/10.3390/molecules18056057 - 21 May 2013

Cited by 27 | Viewed by 7690

Abstract

In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays [...] Read more.

In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71) replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC50 value of 54.57 nM in the MEK1 binding assay. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Low-Density Lipoprotein (LDL)-Antioxidant Biflavonoids from Garcinia madruno

by Edison Osorio, Julián Londoño and Jaume Bastida

Molecules 2013, 18(5), 6092-6100; https://doi.org/10.3390/molecules18056092 - 22 May 2013

Cited by 33 | Viewed by 6285

Abstract

Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl)-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC) spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against [...] Read more.

Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl)-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC) spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against low-density lipoprotein (LDL) peroxidation induced with Cu²⁺, was studied by means of a TBARS assay. The antioxidant potential of a biflavonoid fraction (BF) was also evaluated and correlated with its biflavonoid content. The flavanone-(3→8'')-flavone biflavonoids displayed antioxidant activity, particularly morelloflavone, which was significantly more potent than quercetin, with a CE₅₀ of 12.36 μg/mL. Lipid peroxidation, was also significantly reduced in the presence of the BF (EC₅₀ = 11.85 μg/mL). These results suggest that the BF is an excellent antioxidant. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessShort Note

Bolaamphiphiles Derived from Alkenyl L-Rhamnosides and Alkenyl D-Xylosides: Importance of the Hydrophilic Head

by Sylvain Gatard, Mehmet Nail Nasir, Magali Deleu, Nadia Klai, Vincent Legrand and Sandrine Bouquillon

Molecules 2013, 18(5), 6101-6112; https://doi.org/10.3390/molecules18056101 - 22 May 2013

Cited by 16 | Viewed by 5721

Abstract

The two step synthesis of a new bolaamphiphile derived from alkenyl l-rhamnosides was described. The general synthetic strategy of bolaamphiphiles derived from l-rhamnose was based on a previous work describing the synthesis of bolaamphiphiles derived from d-xylose. The conformational properties of this new [...] Read more.

The two step synthesis of a new bolaamphiphile derived from alkenyl l-rhamnosides was described. The general synthetic strategy of bolaamphiphiles derived from l-rhamnose was based on a previous work describing the synthesis of bolaamphiphiles derived from d-xylose. The conformational properties of this new compound were investigated by FTIR spectroscopy in an aqueous film in order to obtain a reference for further studies about the membrane-interacting properties. Moreover, the surface activity of this new bolaamphiphile was analyzed by Langmuir balance technology and was compared with that of the analogous bolaamphiphile derived from alkenyl D-xylosides. The findings indicate that the rhamnoside-based bolaform has an increased surface activity and a better ability to form aggregates than xyloside-based one. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

The Ameliorative Effect of Sophoricoside on Mast Cell-Mediated Allergic Inflammation in Vivo and in Vitro

by Su-Jin Kim, Gil-Yong Lee, Ji-Wook Jung, Sa-Rang Oh, Eun-Mi Ahn, Sung-Hoon Kim, Seung-Heon Hong and Jae-Young Um

Molecules 2013, 18(5), 6113-6127; https://doi.org/10.3390/molecules18056113 - 22 May 2013

Cited by 17 | Viewed by 8767

Abstract

Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast [...] Read more.

Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases. Full article

(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)

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Review

Jump to: Research

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Open AccessReview

Metabolomics in Adult and Pediatric Nephrology

by Vassilios Fanos, Claudia Fanni, Giovanni Ottonello, Antonio Noto, Angelica Dessì and Michele Mussap

Molecules 2013, 18(5), 4844-4857; https://doi.org/10.3390/molecules18054844 - 24 Apr 2013

Cited by 26 | Viewed by 5587

Abstract

Metabolomics, the latest of the “omics” sciences, has a non-selective approach and can thus lead to the identification of all the metabolites (molecules < 1 kDa) in a biological system. The metabolomic profile can be considered the most predictive phenotype capable of evaluating [...] Read more.

Metabolomics, the latest of the “omics” sciences, has a non-selective approach and can thus lead to the identification of all the metabolites (molecules < 1 kDa) in a biological system. The metabolomic profile can be considered the most predictive phenotype capable of evaluating epigenetic modifications determined by external factors. It is so close to the phenotype as to be considered the phenotype itself in its unique individuality (fingerprinting), both in health (phenome), and disease (diseasome). Urine, compared to other biological liquids, has the advantage of being a complex fluid with many components, including intermediate metabolites. Metabolomics may thus play a role in the study of different kidney diseases and overcome diagnostic difficulties. We shall present the studies that to our knowledge have been published on Nephrology and Pediatric Nephrology. Some are experimental while others are clinical. We have not considered carcinomas and transplantations. Although scarce, the data on adults and the very few ones in pediatrics are quite interesting. Further studies on kidneys are needed to determine the practical clinical impact of metabolomics in kidney renal pathologies. The “multiplatform” “omic” study of urine and namely metabolomics can contribute to improving early diagnosis and the outcome of kidney diseases. Full article

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Open AccessReview

Associations of Volatile Compounds with Sensory Aroma and Flavor: The Complex Nature of Flavor

by Edgar Chambers IV and Kadri Koppel

Molecules 2013, 18(5), 4887-4905; https://doi.org/10.3390/molecules18054887 - 25 Apr 2013

Cited by 160 | Viewed by 13563

Abstract

Attempts to relate sensory analysis data to specific chemicals such as volatile compounds have been frequent. Often these associations are difficult to interpret or are weak in nature. Although some difficulties may relate to the methods used, the difficulties also result from the [...] Read more.

Attempts to relate sensory analysis data to specific chemicals such as volatile compounds have been frequent. Often these associations are difficult to interpret or are weak in nature. Although some difficulties may relate to the methods used, the difficulties also result from the complex nature of flavor. For example, there are multiple volatiles responsible for a flavor sensation, combinations of volatiles yield different flavors than those expected from individual compounds, and the differences in perception of volatiles in different matrices. This review identifies some of the reasons sensory analysis and instrumental measurements result in poor associations and suggests issues that need to be addressed in future research for better understanding of the relationships of flavor/aroma phenomena and chemical composition. Full article

(This article belongs to the Special Issue Flavors and Fragrances)

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Open AccessReview

Folate-Based Radiotracers for PET Imaging—Update and Perspectives

by Cristina Müller

Molecules 2013, 18(5), 5005-5031; https://doi.org/10.3390/molecules18055005 - 29 Apr 2013

Cited by 53 | Viewed by 8399

Abstract

The folate receptor (FR) is expressed in many tumor types, among those ovarian and lung cancer. Due to the high FR affinity of folic acid, it has been used for targeting of FR-positive tumors, allowing specific delivery of attached probes to the malignant [...] Read more.

The folate receptor (FR) is expressed in many tumor types, among those ovarian and lung cancer. Due to the high FR affinity of folic acid, it has been used for targeting of FR-positive tumors, allowing specific delivery of attached probes to the malignant tissue. Therefore, nuclear imaging of FR-positive cancer is of clinical interest for selecting patients who could benefit from innovative therapy concepts based on FR-targeting. Positron emission computed tomography (PET) has become an established technique in clinical routine because it provides an increased spatial resolution and higher sensitivity compared to single photon emission computed tomography (SPECT). Therefore, it is of critical importance to develop folate radiotracers suitable for PET imaging. This review article updates on the design, preparation and pre-clinical investigation of folate derivatives for radiolabeling with radioisotopes for PET. Among those the most relevant radionuclides so far are fluorine-18 (t_1/2: 110 min, E_avβ⁺: 250 keV) and gallium-68 (t_1/2: 68 min, E_av β⁺: 830 keV). Recent results obtained with new PET isotopes such as terbium-152 (t_1/2: 17.5 h, Eβ⁺: 470 keV) or scandium-44 (t_1/2: 3.97 h, E_av β⁺: 632 keV) are also presented and discussed. Current endeavors for clinical implementation of PET agents open new perspectives for identification of FR-positive malignancies in patients. Full article

(This article belongs to the Special Issue PET Chemistry in Molecular Imaging)

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Open AccessReview

Potential Energy Surfaces and Quantum Yields for Photochromic Diarylethene Reactions

by Shinichiro Nakamura, Kingo Uchida and Makoto Hatakeyama

Molecules 2013, 18(5), 5091-5103; https://doi.org/10.3390/molecules18055091 - 2 May 2013

Cited by 29 | Viewed by 6866

Abstract

Photochromic diarylethenes (DAEs) are among the most promising molecular switching systems for future molecular electronics. Numerous derivatives have been synthesized recently, and experimental quantum yields (QYs) have been reported for two categories of them. Although the QY is one of the most important [...] Read more.

Photochromic diarylethenes (DAEs) are among the most promising molecular switching systems for future molecular electronics. Numerous derivatives have been synthesized recently, and experimental quantum yields (QYs) have been reported for two categories of them. Although the QY is one of the most important properties in various applications, it is also the most difficult property to predict before a molecule is actually synthesized. We have previously reported preliminary theoretical studies on what determines the QYs in both categories of DAE derivatives. Here, reflecting theoretical analyses of potential energy surfaces and recent experimental results, a rational explanation of the general guiding principle for QY design is presented for future molecular design. Full article

(This article belongs to the Special Issue New Trends in Photochemistry)

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Open AccessReview

Herb-Herb Combination for Therapeutic Enhancement and Advancement: Theory, Practice and Future Perspectives

by Chun-Tao Che, Zhi Jun Wang, Moses Sing Sum Chow and Christopher Wai Kei Lam

Molecules 2013, 18(5), 5125-5141; https://doi.org/10.3390/molecules18055125 - 3 May 2013

Cited by 159 | Viewed by 12798

Abstract

Herb-herb combinations have been used in Chinese medicine practice for thousands of years, yet scientific evidence of their therapeutic benefits is lacking. With increasing interest in shifting from the one-drug-one-target paradigm to combination therapy or polypharmacy to achieve therapeutic benefits for a number [...] Read more.

Herb-herb combinations have been used in Chinese medicine practice for thousands of years, yet scientific evidence of their therapeutic benefits is lacking. With increasing interest in shifting from the one-drug-one-target paradigm to combination therapy or polypharmacy to achieve therapeutic benefits for a number of diseases, there is momentum to explore new knowledge by tapping the past empirical experiences of herb-herb combinations. This review presents an overview of the traditional concept and practice of herb-herb combination in Chinese medicine, and highlights the available scientific and clinical evidence to support the combined use of herbs. It is hoped that such information would provide a lead for developing new approaches for future therapeutic advancement and pharmaceutical product development. Very likely modern technologies combined with innovative research for the quality control of herbal products, identification of active components and understanding of the molecular mechanism, followed by well-designed animal and clinical studies would pave the way in advancing the wealth of empirical knowledge from herb-herb combination to new therapeutic modalities. Full article

(This article belongs to the Special Issue Phytochemicals: Analytical and Medicinal Chemistry)

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Open AccessReview

From Selenium- to Tellurium-Based Glass Optical Fibers for Infrared Spectroscopies

by Shuo Cui, Radwan Chahal, Catherine Boussard-Plédel, Virginie Nazabal, Jean-Louis Doualan, Johann Troles, Jacques Lucas and Bruno Bureau

Molecules 2013, 18(5), 5373-5388; https://doi.org/10.3390/molecules18055373 - 10 May 2013

Cited by 76 | Viewed by 8725

Abstract

Chalcogenide glasses are based on sulfur, selenium and tellurium elements, and have been studied for several decades regarding different applications. Among them, selenide glasses exhibit excellent infrared transmission in the 1 to 15 µm region. Due to their good thermo-mechanical properties, these glasses [...] Read more.

Chalcogenide glasses are based on sulfur, selenium and tellurium elements, and have been studied for several decades regarding different applications. Among them, selenide glasses exhibit excellent infrared transmission in the 1 to 15 µm region. Due to their good thermo-mechanical properties, these glasses could be easily shaped into optical devices such as lenses and optical fibers. During the past decade of research, selenide glass fibers have been proved to be suitable for infrared sensing in an original spectroscopic method named Fiber Evanescent Wave Spectroscopy (FEWS). FEWS has provided very nice and promising results, for example for medical diagnosis. Then, some sophisticated fibers, also based on selenide glasses, were developed: rare-earth doped fibers and microstructured fibers. In parallel, the study of telluride glasses, which can have transmission up to 28 µm due to its atom heaviness, has been intensified thanks to the DARWIN mission led by the European Space Agency (ESA). The development of telluride glass fiber enables a successful observation of CO₂ absorption band located around 15 µm. In this paper we review recent results obtained in the Glass and Ceramics Laboratory at Rennes on the development of selenide to telluride glass optical fibers, and their use for spectroscopy from the mid to the far infrared ranges. Full article

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Camphor—A Fumigant during the Black Death and a Coveted Fragrant Wood in Ancient Egypt and Babylon—A Review

by Weiyang Chen, Ilze Vermaak and Alvaro Viljoen

Molecules 2013, 18(5), 5434-5454; https://doi.org/10.3390/molecules18055434 - 10 May 2013

Cited by 203 | Viewed by 25266

Abstract

The fragrant camphor tree (Cinnamomum camphora) and its products, such as camphor oil, have been coveted since ancient times. Having a rich history of traditional use, it was particularly used as a fumigant during the era of the Black Death and [...] Read more.

The fragrant camphor tree (Cinnamomum camphora) and its products, such as camphor oil, have been coveted since ancient times. Having a rich history of traditional use, it was particularly used as a fumigant during the era of the Black Death and considered as a valuable ingredient in both perfume and embalming fluid. Camphor has been widely used as a fragrance in cosmetics, as a food flavourant, as a common ingredient in household cleaners, as well as in topically applied analgesics and rubefacients for the treatment of minor muscle aches and pains. Camphor, traditionally obtained through the distillation of the wood of the camphor tree, is a major essential oil component of many aromatic plant species, as it is biosynthetically synthesised; it can also be chemically synthesised using mainly turpentine as a starting material. Camphor exhibits a number of biological properties such as insecticidal, antimicrobial, antiviral, anticoccidial, anti-nociceptive, anticancer and antitussive activities, in addition to its use as a skin penetration enhancer. However, camphor is a very toxic substance and numerous cases of camphor poisoning have been documented. This review briefly summarises the uses and synthesis of camphor and discusses the biological properties and toxicity of this valuable molecule. Full article

(This article belongs to the Special Issue Flavors and Fragrances)

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Open AccessReview

Isotope Effects as Probes for Enzyme Catalyzed Hydrogen-Transfer Reactions

by Daniel Roston, Zahidul Islam and Amnon Kohen

Molecules 2013, 18(5), 5543-5567; https://doi.org/10.3390/molecules18055543 - 14 May 2013

Cited by 44 | Viewed by 10101

Abstract

Kinetic Isotope effects (KIEs) have long served as a probe for the mechanisms of both enzymatic and solution reactions. Here, we discuss various models for the physical sources of KIEs, how experimentalists can use those models to interpret their data, and how the [...] Read more.

Kinetic Isotope effects (KIEs) have long served as a probe for the mechanisms of both enzymatic and solution reactions. Here, we discuss various models for the physical sources of KIEs, how experimentalists can use those models to interpret their data, and how the focus of traditional models has grown to a model that includes motion of the enzyme and quantum mechanical nuclear tunneling. We then present two case studies of enzymes, thymidylate synthase and alcohol dehydrogenase, and discuss how KIEs have shed light on the C-H bond cleavages those enzymes catalyze. We will show how the combination of both experimental and computational studies has changed our notion of how these enzymes exert their catalytic powers. Full article

(This article belongs to the Collection Isotope Effects)

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Open AccessReview

Chitosan for Gene Delivery and Orthopedic Tissue Engineering Applications

by Rosanne Raftery, Fergal J. O'Brien and Sally-Ann Cryan

Molecules 2013, 18(5), 5611-5647; https://doi.org/10.3390/molecules18055611 - 15 May 2013

Cited by 143 | Viewed by 14785

Abstract

Gene therapy involves the introduction of foreign genetic material into cells in order exert a therapeutic effect. The application of gene therapy to the field of orthopaedic tissue engineering is extremely promising as the controlled release of therapeutic proteins such as bone morphogenetic [...] Read more.

Gene therapy involves the introduction of foreign genetic material into cells in order exert a therapeutic effect. The application of gene therapy to the field of orthopaedic tissue engineering is extremely promising as the controlled release of therapeutic proteins such as bone morphogenetic proteins have been shown to stimulate bone repair. However, there are a number of drawbacks associated with viral and synthetic non-viral gene delivery approaches. One natural polymer which has generated interest as a gene delivery vector is chitosan. Chitosan is biodegradable, biocompatible and non-toxic. Much of the appeal of chitosan is due to the presence of primary amine groups in its repeating units which become protonated in acidic conditions. This property makes it a promising candidate for non-viral gene delivery. Chitosan-based vectors have been shown to transfect a number of cell types including human embryonic kidney cells (HEK293) and human cervical cancer cells (HeLa). Aside from its use in gene delivery, chitosan possesses a range of properties that show promise in tissue engineering applications; it is biodegradable, biocompatible, has anti-bacterial activity, and, its cationic nature allows for electrostatic interaction with glycosaminoglycans and other proteoglycans. It can be used to make nano- and microparticles, sponges, gels, membranes and porous scaffolds. Chitosan has also been shown to enhance mineral deposition during osteogenic differentiation of MSCs in vitro. The purpose of this review is to critically discuss the use of chitosan as a gene delivery vector with emphasis on its application in orthopedic tissue engineering. Full article

(This article belongs to the Special Issue Chitins and Chitosans)

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373 KiB

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Vasodilator Compounds Derived from Plants and Their Mechanisms of Action

by Francisco J. Luna-Vázquez, César Ibarra-Alvarado, Alejandra Rojas-Molina, Isela Rojas-Molina and Miguel Ángel Zavala-Sánchez

Molecules 2013, 18(5), 5814-5857; https://doi.org/10.3390/molecules18055814 - 17 May 2013

Cited by 56 | Viewed by 10418

Abstract

The present paper reviews vasodilator compounds isolated from plants that were reported in the past 22 years (1990 to 2012) and the different mechanisms of action involved in their vasodilator effects. The search for reports was conducted in a comprehensive manner, intending to [...] Read more.

The present paper reviews vasodilator compounds isolated from plants that were reported in the past 22 years (1990 to 2012) and the different mechanisms of action involved in their vasodilator effects. The search for reports was conducted in a comprehensive manner, intending to encompass those metabolites with a vasodilator effect whose mechanism of action involved both vascular endothelium and arterial smooth muscle. The results obtained from our bibliographic search showed that over half of the isolated compounds have a mechanism of action involving the endothelium. Most of these bioactive metabolites cause vasodilation either by activating the nitric oxide/cGMP pathway or by blocking voltage-dependent calcium channels. Moreover, it was found that many compounds induced vasodilation by more than one mechanism. This review confirms that secondary metabolites, which include a significant group of compounds with extensive chemical diversity, are a valuable source of new pharmaceuticals useful for the treatment and prevention of cardiovascular diseases. Full article

(This article belongs to the Special Issue Bioassay-Guided Isolation of Natural Products)

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Open AccessReview

Gold Nanoparticle Contrast Agents in Advanced X-ray Imaging Technologies

by Sungsook Ahn, Sung Yong Jung and Sang Joon Lee

Molecules 2013, 18(5), 5858-5890; https://doi.org/10.3390/molecules18055858 - 17 May 2013

Cited by 92 | Viewed by 12509

Abstract

Recently, there has been significant progress in the field of soft- and hard-X-ray imaging for a wide range of applications, both technically and scientifically, via developments in sources, optics and imaging methodologies. While one community is pursuing extensive applications of available X-ray tools, [...] Read more.

Recently, there has been significant progress in the field of soft- and hard-X-ray imaging for a wide range of applications, both technically and scientifically, via developments in sources, optics and imaging methodologies. While one community is pursuing extensive applications of available X-ray tools, others are investigating improvements in techniques, including new optics, higher spatial resolutions and brighter compact sources. For increased image quality and more exquisite investigation on characteristic biological phenomena, contrast agents have been employed extensively in imaging technologies. Heavy metal nanoparticles are excellent absorbers of X-rays and can offer excellent improvements in medical diagnosis and X-ray imaging. In this context, the role of gold (Au) is important for advanced X-ray imaging applications. Au has a long-history in a wide range of medical applications and exhibits characteristic interactions with X-rays. Therefore, Au can offer a particular advantage as a tracer and a contrast enhancer in X-ray imaging technologies by sensing the variation in X-ray attenuation in a given sample volume. This review summarizes basic understanding on X-ray imaging from device set-up to technologies. Then this review covers recent studies in the development of X-ray imaging techniques utilizing gold nanoparticles (AuNPs) and their relevant applications, including two- and three-dimensional biological imaging, dynamical processes in a living system, single cell-based imaging and quantitative analysis of circulatory systems and so on. In addition to conventional medical applications, various novel research areas have been developed and are expected to be further developed through AuNP-based X-ray imaging technologies. Full article

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362 KiB

Open AccessReview

Metabolites from Alternaria Fungi and Their Bioactivities

by Jingfeng Lou, Linyun Fu, Youliang Peng and Ligang Zhou

Molecules 2013, 18(5), 5891-5935; https://doi.org/10.3390/molecules18055891 - 21 May 2013

Cited by 215 | Viewed by 15509

Abstract

Alternaria is a cosmopolitan fungal genus widely distributing in soil and organic matter. It includes saprophytic, endophytic and pathogenic species. At least 268 metabolites from Alternaria fungi have been reported in the past few decades. They mainly include nitrogen-containing metabolites, steroids, terpenoids, pyranones, [...] Read more.

Alternaria is a cosmopolitan fungal genus widely distributing in soil and organic matter. It includes saprophytic, endophytic and pathogenic species. At least 268 metabolites from Alternaria fungi have been reported in the past few decades. They mainly include nitrogen-containing metabolites, steroids, terpenoids, pyranones, quinones, and phenolics. This review aims to briefly summarize the structurally different metabolites produced by Alternaria fungi, as well as their occurrences, biological activities and functions. Some considerations related to synthesis, biosynthesis, production and applications of the metabolites from Alternaria fungi are also discussed. Full article

(This article belongs to the Section Natural Products Chemistry)

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Molecules, Volume 18, Issue 5 (May 2013) – 81 articles , Pages 4844-6127

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