Molecules

16 pages, 538 KiB

Open AccessArticle

Identification of Dehydroxytrichostatin A as a Novel Up-Regulator of the ATP-Binding Cassette Transporter A1 (ABCA1)

by Yang Xu^†, Yanni Xu^†, Yi Bao, Bin Hong^* and Shuyi Si^*

¹ Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China

^† These authors contributed equally to this work.

Molecules 2011, 16(9), 7183-7198; https://doi.org/10.3390/molecules16097183 - 25 Aug 2011

Cited by 18 | Viewed by 7395

Abstract

The ATP-binding cassette transporter A1 (ABCA1) mediates the cellular efflux of excess cholesterol and phospholipids to lipid-poor apolipoprotein A-I (apoA-I). ABCA1 plays an important role in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. By using a cell-based screening model for the ABCA1 [...] Read more.

The ATP-binding cassette transporter A1 (ABCA1) mediates the cellular efflux of excess cholesterol and phospholipids to lipid-poor apolipoprotein A-I (apoA-I). ABCA1 plays an important role in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. By using a cell-based screening model for the ABCA1 up-regulator and column chromatography, an active compound, 9179B, was isolated. Through analysis of its NMR data, 9179B was identified as dehydroxytrichostatin A. We found that 9179B increased the transcription of ABCA1 in a cell-based reporter assay, with an EC₅₀ value of 2.65 μM. 9179B up-regulated ABCA1 expression at both mRNA and protein levels in HepG2 and RAW264.7 cells. It also up-regulated the expression of scavenger receptor class B type I (SR-BI) as well as the uptake of DiI-HDL in RAW264.7 cells. This compound stimulated ApoA-I-mediated cellular cholesterol efflux from RAW 264.7 cells. We further found that 9179B was a potent histone deacetylase (HDAC) inhibitor with an IC₅₀ value of 0.08 μM. Reporter gene assays showed that the regulation of ABCA1 transcription by 9179B was mainly mediated by the −171/−75 bp promoter region. Together, our results indicate that 9179B is an ABCA1 up-regulator and dehydroxytrichostatin A may be a novel anti-atherogenic compound. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 554 KiB

Open AccessArticle

Chirality and Numbering of Substituted Tropane Alkaloids

by Munir Humam¹, Tarik Shoul¹, Damien Jeannerat², Orlando Muñoz³ and Philippe Christen^1,*

¹ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland

² Department of Organic Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland

³ Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile

Molecules 2011, 16(9), 7199-7209; https://doi.org/10.3390/molecules16097199 - 25 Aug 2011

Cited by 14 | Viewed by 8013

Abstract

The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based [...] Read more.

The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based on NMR and MS data, without taking into account the absolute configuration of these two carbons. This paper discusses the problem and the relevance of CD and NMR to determine molecular configurations. We report on the use of ¹H-NMR anisochrony (Δd) induced by the Mosher’s chiral auxiliary reagents (R)-(-)- and (S)-(+)-α-methoxy-α-trifluoromethyl-phenylacetyl chlorides (MTPA-Cl), to determine the absolute configuration of (3R,6R)-3α-hydroxy-6b-senecioyloxytropane, a disubstituted tropane alkaloid isolated from the aerial parts of Schizanthus grahamii (Solanaceae). These analytical tools should help future works in correctly assigning the configuration of additional 3, 6/7 disubstituted tropane derivatives. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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14 pages, 551 KiB

Open AccessArticle

Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes

by Kiyomitsu Katsumata, Koji Chono, Kenji Sudo, Yasuaki Shimizu, Toru Kontani and Hiroshi Suzuki^*

Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki, Japan

Molecules 2011, 16(9), 7210-7223; https://doi.org/10.3390/molecules16097210 - 25 Aug 2011

Cited by 27 | Viewed by 8513

Abstract

ASP2151 is a herpesvirus helicase-primase inhibitor with antiviral activity against varicella zoster virus and herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Here, we examined the potency and efficacy of ASP2151 against HSV in vitro and in vivo. We found that [...] Read more.

ASP2151 is a herpesvirus helicase-primase inhibitor with antiviral activity against varicella zoster virus and herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Here, we examined the potency and efficacy of ASP2151 against HSV in vitro and in vivo. We found that ASP2151 was more potent in inhibiting the replication of HSV-1 and HSV-2 in Vero cells in the plaque reduction assay and had greater anti-HSV activity in a guinea pig model of genital herpes than did acyclovir and valacyclovir (VACV), respectively. Oral ASP2151 given from the day of infection reduced peak and overall disease scores in a dose-dependent manner, resulting in complete prevention of symptoms at the dose of 30 mg/kg. The 50% effective dose (ED₅₀) values for ASP2151 and VACV were 0.37 and 68 mg/kg, respectively, indicating that ASP2151 was 184-fold more potent than VACV. When ASP2151 was administered after the onset of symptoms, the disease course of genital herpes was suppressed more effectively than by VACV, with a significant reduction in disease score observed one day after starting ASP2151 at 30 mg/kg, whereas the therapeutic effect of VACV was only evident three days after treatment at the highest dose tested (300 mg/kg). This indicated that ASP2151 possesses a faster onset of action and wider therapeutic time window than VACV. Further, virus shedding from the genital mucosa was significantly reduced with ASP2151 at 10 and 30 mg/kg but not with VACV, even at 300 mg/kg. Taken together, our present findings demonstrated the superior potency and efficacy of ASP2151 against HSV. Full article

(This article belongs to the Special Issue Antivirals)

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13 pages, 622 KiB

Open AccessArticle

Flow Injection Spectrophotometric Determination of N-Acetyl-L-cysteine as a Complex with Palladium(II)

by Josipa Giljanović^1,*, Mia Brkljača² and Ante Prkić¹

¹ Department of Analytical Chemistry, Faculty of Chemistry and Technology, Teslina 10/V, 21000 Split, Croatia

² Department of Mediterranean Agriculture and Aquaculture, University of Zadar, Mihovila Pavlinovića bb, 23000 Zadar, Croatia

Molecules 2011, 16(9), 7224-7236; https://doi.org/10.3390/molecules16097224 - 25 Aug 2011

Cited by 17 | Viewed by 7594

Abstract

We describe a new method using flow-injection analysis with spectro-photometric detection, suitable for the determination of N-acetyl-L-cysteine (NAC). The proposed method is appropriate for the determination of NAC in reaction with Pd²⁺ ions in the concentration range from 1.0 × 10 [...] Read more.

We describe a new method using flow-injection analysis with spectro-photometric detection, suitable for the determination of N-acetyl-L-cysteine (NAC). The proposed method is appropriate for the determination of NAC in reaction with Pd²⁺ ions in the concentration range from 1.0 × 10⁻⁵ mol L⁻¹ to 6.0 × 10⁻⁵ mol L⁻¹. The detection limit NAC was 5.84 × 10⁻⁶ mol L⁻¹ and the recorded relative standard deviation of the method is in the range from 1.67 to 4.11%. NAC and Pd²⁺ form complexes of Pd²⁺:NAC molar ratios of 1:1 and 1:2, depending on the ratio of their analytical concentrations. The cumulative conditional stability constant for the Pd(NAC)₂²⁺ complex is β₁₂' = 2.69 × 10⁹ L² mol⁻². The proposed method was compared with the classic spectrophotometric determination of NAC, using the same reagent, PdCl₂, and had shown certain advantages: a) shorter analysis time; b) the use of smaller volumes of sample and reagents, which make the proposed method cheaper and faster for NAC determination in real samples without sample pretreatment. Full article

(This article belongs to the Special Issue Flow Chemistry)

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12 pages, 1564 KiB

Open AccessArticle

Synthesis of Silver Nanoparticles in Chitosan, Gelatin and Chitosan/Gelatin Bionanocomposites by a Chemical Reducing Agent and Their Characterization

by Mansor Bin Ahmad^*, Jenn Jye Lim, Kamyar Shameli, Nor Azowa Ibrahim and Mei Yen Tay

Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

Molecules 2011, 16(9), 7237-7248; https://doi.org/10.3390/molecules16097237 - 25 Aug 2011

Cited by 197 | Viewed by 14238

Abstract

In this research, silver nanoparticles (AgNPs) were synthesized in chitosan (Cts), Cts/gelatin and gelatin suspensions using a chemical reducing agent. Cts and gelatin were used as natural stabilizers and solid support, whereas AgNO₃ was used as the silver precursor. Sodium borohydride (NaBH [...] Read more.

In this research, silver nanoparticles (AgNPs) were synthesized in chitosan (Cts), Cts/gelatin and gelatin suspensions using a chemical reducing agent. Cts and gelatin were used as natural stabilizers and solid support, whereas AgNO₃ was used as the silver precursor. Sodium borohydride (NaBH₄) was used as the reducing agent. The properties of AgNPs in Cts, Cts/gelatin and gelatin bionanocomposites (BNCs) were studied in terms of their surface plasmon resonance, crystalline structure, average diameter size, particle distributions, surface topography and functional groups. All the samples were characterized by UV-visible spectroscopy, powder X-ray diffraction, transmission electron microscopy, atomic force microscopy and Fourier transform infrared spectroscopy. Full article

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7 pages, 492 KiB

Open AccessArticle

A Novel Cyclodione Coumarin from the Stem Bark of Mesua beccariana

by Gwendoline Cheng Lian Ee^1,*, Soek Sin Teh¹, Siau Hui Mah¹, Mawardi Rahmani¹, Yun Hin Taufiq-Yap¹ and Khalijah Awang²

¹ Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia

² Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

Molecules 2011, 16(9), 7249-7255; https://doi.org/10.3390/molecules16097249 - 25 Aug 2011

Cited by 8 | Viewed by 5610

Abstract

Our ongoing investigations on the stem bark of Mesua beccariana afforded a novel cyclodione coumarin, beccamarin, together with two known xanthones, mesuarianone, mesuasinone, two anthraquinones, 4-methoxy-1,3,5-trihydroxy-anthraquinone and 2,5-dihydroxy-1,3,4-trimethoxyanthraquinone and one coumarin, mammea A/AB. The structures were elucidated by 1D and 2D NMR [...] Read more.

Our ongoing investigations on the stem bark of Mesua beccariana afforded a novel cyclodione coumarin, beccamarin, together with two known xanthones, mesuarianone, mesuasinone, two anthraquinones, 4-methoxy-1,3,5-trihydroxy-anthraquinone and 2,5-dihydroxy-1,3,4-trimethoxyanthraquinone and one coumarin, mammea A/AB. The structures were elucidated by 1D and 2D NMR and MS techniques. Full article

(This article belongs to the Special Issue Coumarins and Xanthones)

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11 pages, 391 KiB

Open AccessArticle

Use of Graphite Oxide and Graphene Oxide as Catalysts in the Synthesis of Dipyrromethane and Calix[4]pyrrole

by Shive Murat Singh Chauhan^* and Sweta Mishra

Bioorganic Research Laboratory, Department of Chemistry, University of Delhi, Delhi-110007, India

Molecules 2011, 16(9), 7256-7266; https://doi.org/10.3390/molecules16097256 - 25 Aug 2011

Cited by 67 | Viewed by 11235

Abstract

Graphite oxide and graphene oxides have been used as solid catalysts for the synthesis of 5,5-dialkyldipyrromethanes and calix[4]pyrroles in organic and aqueous solutions at room temperature. Full article

(This article belongs to the Section Organic Chemistry)

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21 pages, 922 KiB

Open AccessArticle

Cyclization vs. Cyclization/Dimerization in o-Amidostilbene Radical Cation Cascade Reactions: The Amide Question

by Chin Hui Kee¹, Azhar Ariffin¹, Khalijah Awang¹, Ibrahim Noorbatcha², Koichi Takeya³, Hiroshi Morita⁴, Chuan Gee Lim⁵ and Noel Francis Thomas^1,*

¹ Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

² Department of Biotechnology Engineering, Faculty of Engineering, International Islamic University Malaysia, 53100 Kuala Lumpur, Malaysia

³ Department of Pharmacognosy, Tokyo University of Pharmaceutical and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

⁴ Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan

⁵ Environmental and Bioprocess Technology Centre, SIRIM Berhad, 40000 Shah Alam, Malaysia

Molecules 2011, 16(9), 7267-7287; https://doi.org/10.3390/molecules16097267 - 25 Aug 2011

Cited by 7 | Viewed by 8421

Abstract

The n-butyramido, isobutyramido, benzamido, and furancarboxamido functions profoundly modulate the electronics of the stilbene olefinic and NH groups and the corresponding radical cations in ways that influence the efficiency of the cyclization due presumably to conformational and stereoelectronic factors. For example, isobutyramido- [...] Read more.

The n-butyramido, isobutyramido, benzamido, and furancarboxamido functions profoundly modulate the electronics of the stilbene olefinic and NH groups and the corresponding radical cations in ways that influence the efficiency of the cyclization due presumably to conformational and stereoelectronic factors. For example, isobutyramido- stilbene undergoes FeCl₃ promoted cyclization to produce only indoline, while n-butyramidostilbene, under the same conditions, produces both indoline and bisindoline. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 495 KiB

Open AccessArticle

Development of a Process for Separation of Mogroside V from Siraitia grosvenorii by Macroporous Resins

by Min Zhang¹, Huihua Yang^2,*, Hongyang Zhang³, Yuerong Wang³ and Ping Hu^3,*

¹ Modern Engineering Center for Traditional Chinese Medicine, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

² College of Computer Science and Control, Guilin University of Electronic Technology, Guilin 541004, China

³ School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China

Molecules 2011, 16(9), 7288-7301; https://doi.org/10.3390/molecules16097288 - 25 Aug 2011

Cited by 19 | Viewed by 7588

Abstract

A separation method was developed for the preparative separation and enrichment of the non-caloric sweetener mogroside V from Siraitia grosvenorii. The adsorption properties of six macroporous resins were evaluated. Results showed that HZ 806 resin offered the best adsorption and desorption capacities. [...] Read more.

A separation method was developed for the preparative separation and enrichment of the non-caloric sweetener mogroside V from Siraitia grosvenorii. The adsorption properties of six macroporous resins were evaluated. Results showed that HZ 806 resin offered the best adsorption and desorption capacities. Based on the adsorption experiments on HZ 806, the adsorption data were found to fit the Freundlich model well. The pseudo-second-order kinetic model showed the highest correlation with the experimental results. Separation was performed with deionized water and 40% aqueous ethanol solution as mobile phases. In a typical run, 100 g of herb was processed and 3.38 g of mogroside V with a purity of 10.7% was harvested. This separation method provided a 15.1-fold increase in the purification factor from 0.5% to 10.7%. The present study showed that HZ 806 resins were effective for the separation and enrichment of mogroside V from S. grosvenorii. Full article

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18 pages, 465 KiB

Open AccessArticle

Antioxidant and Antimicrobial Attributes and Phenolics of Different Solvent Extracts from Leaves, Flowers and Bark of Gold Mohar [Delonix regia (Bojer ex Hook.) Raf.]

by Ghulam Shabir^1,2, Farooq Anwar^1,*, Bushra Sultana¹, Zafar M. Khalid², Muhammad Afzal², Qaiser M. Khan² and M. Ashrafuzzaman^3,*

¹ Department of Chemistry and Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan

² Environmental Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), P.O.Box 577, Jhang Road, Faisalabad, Pakistan

³ Institute of Tropical Agriculture, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Malaysia

Molecules 2011, 16(9), 7302-7319; https://doi.org/10.3390/molecules16097302 - 25 Aug 2011

Cited by 114 | Viewed by 12137

Abstract

This paper describes the antioxidant and antimicrobial activities and phenolic components of different solvent (absolute methanol, absolute ethanol, absolute acetone, 80% methanol, 80% ethanol, 80% acetone and deionized water) extracts of leaves, flowers and bark of Gold Mohar [Delonix regia (Bojer ex [...] Read more.

This paper describes the antioxidant and antimicrobial activities and phenolic components of different solvent (absolute methanol, absolute ethanol, absolute acetone, 80% methanol, 80% ethanol, 80% acetone and deionized water) extracts of leaves, flowers and bark of Gold Mohar [Delonix regia (Bojer ex Hook.) Raf.]. The extract yields from leaves, flowers and bark ranged from 10.19 to 36.24, 12.97 to 48.47 and 4.22 to 8.48 g/100 g dry weight (DW), respectively. Overall, 80% methanol extract produced from the leaves exhibited significantly (P < 0.05) higher antioxidant activity, with high phenolic contents (3.63 g GAE/100 g DW), total flavonoid contents (1.19 g CE/100 g DW), inhibition of peroxidation (85.54%), DPPH scavenging capacity (IC₅₀ value 8.89 μg/mL) and reducing power (1.87). Similarly, this 80% methanol leaves extract also showed superior antimicrobial activity. HPLC analysis of the 80% methanol extracts for individual phenolics revealed the presence of gallic, protocatechuic and salicylic acid in leaves; gallic, protocatechuic, salicylic, trans-cinnamic and chlorogenic acid in flowers, and gallic acid in bark as the main (amount > 1.50 mg/100 g DW) phenolic acids. Besides, small amounts ( < 1.50 mg/100 g DW) of some other phenolic acids such as sorbic, sinapic, p-coumaric, m-coumaric, ferulic, caffeic, 3-hydroxybenzoic, 4-hydroxycinnamic and 4-hydroxybenzoic acids were also detected. The extracts of the tested parts of Gold Mohar, especially, the leaves, might be valuable for functional food and therapeutic applications. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 420 KiB

Open AccessArticle

Toxicity of Rhododendron anthopogonoides Essential Oil and Its Constituent Compounds towards Sitophilus zeamais

by Kai Yang¹, Yu Xin Zhou^2,*, Cheng Fang Wang³, Shu Shan Du³, Zhi Wei Deng⁴, Qi Zhi Liu¹ and Zhi Long Liu^1,*

¹ Department of Entomology, China Agricultural University, Haidian District, Beijing 100193, China

² Institute of Chinese Materia Medica, Henan University, Kaifeng 475001, China

³ State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China

⁴ Analytical and Testing Center, Beijing Normal University, Beijing 100875, China

Molecules 2011, 16(9), 7320-7330; https://doi.org/10.3390/molecules16097320 - 25 Aug 2011

Cited by 46 | Viewed by 8560

Abstract

The screening of several Chinese medicinal plants for insecticidal principles showed that essential oil of Rhododendron anthopogonoides flowering aerial parts possessed significant toxicity against maize weevils, Sitophilus zeamais. A total of 37 components were identified in the essential oil and the main [...] Read more.

The screening of several Chinese medicinal plants for insecticidal principles showed that essential oil of Rhododendron anthopogonoides flowering aerial parts possessed significant toxicity against maize weevils, Sitophilus zeamais. A total of 37 components were identified in the essential oil and the main constituents of the essential oil were 4-phenyl-2-butanone (27.22%), nerolidol (8.08%), 1,4-cineole (7.85%), caryophyllene (7.63%) and γ-elemene (6.10%), followed by α-farnesene (4.40%) and spathulenol (4.19%). Repeated bioactivity-directed chromatographic separation on silica gel columns led us to isolate three compounds, namely 4-phenyl-2-butanone, 1,4-cineole, and nerolidol. 4-Phenyl-2-butanone shows pronounced contact toxicity against S. zeamais (LD₅₀ = 6.98 mg/adult) and was more toxic than either 1,4-cineole or nerolidol (LD₅₀ = 50.86 mg/adult and 29.30 mg/adult, respectively) against the maize weevils, while the crude essential oil had a LD₅₀ value of 11.67 mg/adult. 4-Phenyl-2-butanone and 1,4-cineole also possessed strong fumigant toxicity against the adults of S. zeamais (LC₅₀ = 3.80 mg/L and 21.43 mg/L) while the crude essential oil had a LC₅₀ value of 9.66 mg/L. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 548 KiB

Open AccessArticle

Interaction of α-Melanocortin and Its Pentapeptide Antisense LVKAT: Effects on Hepatoprotection in Male CBA Mice

by Karlo Houra¹, Petra Turčić²

, Mario Gabričević³, Tin Weitner³, Paško Konjevoda⁴ and Nikola Štambuk^4,*

¹ St. Catherine’s Hospital, Bračak 8, 49210 Zabok, Croatia

² Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Domagojeva 2, 10000 Zagreb, Croatia

³ Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia

⁴ Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia

Molecules 2011, 16(9), 7331-7343; https://doi.org/10.3390/molecules16097331 - 26 Aug 2011

Cited by 11 | Viewed by 5634

Abstract

The genetic code defines nucleotide patterns that code for individual amino acids and their complementary, i.e., antisense, pairs. Peptides specified by the complementary mRNAs often bind to each other with a higher specificity and efficacy. Applications of this genetic code property in [...] Read more.

The genetic code defines nucleotide patterns that code for individual amino acids and their complementary, i.e., antisense, pairs. Peptides specified by the complementary mRNAs often bind to each other with a higher specificity and efficacy. Applications of this genetic code property in biomedicine are related to the modulation of peptide and hormone biological function, selective immunomodulation, modeling of discontinuous and linear epitopes, modeling of mimotopes, paratopes and antibody mimetics, peptide vaccine development, peptidomimetic and drug design. We have investigated sense-antisense peptide interactions and related modulation of the peptide function by modulating the effects of a-MSH on hepatoprotection with its antisense peptide LVKAT. First, transcription of complementary mRNA sequence of a-MSH in 3’→5’ direction was used to design antisense peptide to the central motif that serves as a-MSH pharmacophore for melanocortin receptors. Second, tryptophan spectrofluorometric titration was applied to evaluate the binding of a-MSH and its central pharmacophore motif to the antisense peptide, and it was concluded that this procedure represents a simple and efficient method to evaluate sense-antisense peptide interaction in vitro. Third, we showed that antisense peptide LVKAT abolished potent hepatoprotective effects of a-MSH in vivo. Full article

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13 pages, 492 KiB

Open AccessArticle

Evaluation of the Effects of Mitragyna speciosa Alkaloid Extract on Cytochrome P450 Enzymes Using a High Throughput Assay

by Wai Mun Kong^1,2,*, Zamri Chik¹, Murali Ramachandra³, Umarani Subramaniam², Raja Elina Raja Aziddin⁴ and Zahurin Mohamed¹

¹ Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

² Aurigene Discovery Technologies (M) Sdn. Bhd, Malaysia, 57000 Bukit Jalil, Kuala Lumpur, Malaysia

³ Aurigene Discovery Technologies Limited, Bangalore 560100, Karnataka, India

⁴ Department of Pathology, Hospital Kuala Lumpur, 50586 Kuala Lumpur, Malaysia

Molecules 2011, 16(9), 7344-7356; https://doi.org/10.3390/molecules16097344 - 29 Aug 2011

Cited by 71 | Viewed by 13853

Abstract

The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi [...] Read more.

The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost-effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC₅₀) values of 0.78 µg/mL and 0.636 µg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC₅₀ of 39 µg/mL, and weak inhibition was detected for CYP2C19. The IC₅₀ of CYP2C19 could not be determined, however, because inhibition was < 50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were used as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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8 pages, 353 KiB

Open AccessArticle

Antibacterial Activity of Aristolochia brevipes against Multidrug-Resistant Mycobacterium tuberculosis

by Víctor Manuel Navarro-García^1,*, Julieta Luna-Herrera², Ma. Gabriela Rojas-Bribiesca¹, Patricia Álvarez-Fitz¹ and María Yolanda Ríos³

¹ Laboratory of Microbiology, Biomedical Research Center of the South (IMSS), Argentina 1, Col. Centro, 62790 Xochitepec, Morelos, Mexico

² Immunochemistry Laboratory II, Department of Immunology, National School of Sciences Bilogy (IPN), Prolongación Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomás, 11340 Mexico, D.F., Mexico

³ Chemical Research Center, University of Morelos (UAEM), Av. Universidad 1001, Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico

Molecules 2011, 16(9), 7357-7364; https://doi.org/10.3390/molecules16097357 - 29 Aug 2011

Cited by 44 | Viewed by 9559

Abstract

The increased incidence of Multidrug-Resistant Mycobacterium tuberculosis (MDR-MT) requires the search for alternative antimycobacterial drugs. The main aim of this study was to evaluate the dichloromethane extract from Aristolochia brevipes (Rhizoma) and the compounds isolated from this extract against several mycobacterial strains, sensitive, [...] Read more.

The increased incidence of Multidrug-Resistant Mycobacterium tuberculosis (MDR-MT) requires the search for alternative antimycobacterial drugs. The main aim of this study was to evaluate the dichloromethane extract from Aristolochia brevipes (Rhizoma) and the compounds isolated from this extract against several mycobacterial strains, sensitive, resistant (monoresistant), and clinical isolates (multidrug-resistant), using the alamarBlue™ microassay. The extract was fractionated by column chromatography, yielding the following eight major compounds: (1) 6α-7-dehydro-N-formylnornantenine; (2) E/Z-N-formylnornantenine; (3) 7,9-dimethoxytariacuripyrone; (4) 9-methoxy-tariacuripyrone; (5) aristololactam I; (6) β-sitosterol; (7) stigmasterol; and (8) 3-hydroxy-α-terpineol. The structures of these compounds were elucidated by ¹H- and ¹³C- (1D and 2D) Nuclear Magnetic Resonance (NMR) spectroscopy. This study demonstrates that the dichloromethane extract (rhizome) of A. brevipes possesses strong in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL). The most active compound against all mycobacterial strains tested was the compound aristolactam I (5), with MIC values ranging between 12.5 and 25 µg/mL. To our knowledge, this the first report of antimycobacterial activity in this plant. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1023 KiB

Open AccessArticle

An Emulsion Based Microarray Method to Detect the Toxin Genes of Toxin-Producing Organisms

by Ying Wang¹, Jiafeng Lu², Qi Yang², Yunfei Bai² and Qinyu Ge^1,*

¹ Key Laboratory of Child Development and Learning Science, Ministry of Education, Southeast University, Nanjing 210096, China

² State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China

Molecules 2011, 16(9), 7365-7376; https://doi.org/10.3390/molecules16097365 - 29 Aug 2011

Cited by 2 | Viewed by 5637

Abstract

Toxins produced by bacteria and fungi are one of the most important factors which may cause food contamination. The study of detection methods with high sensitivity and throughput is significant for the protection of food safety. In the present study, we coupled microarray [...] Read more.

Toxins produced by bacteria and fungi are one of the most important factors which may cause food contamination. The study of detection methods with high sensitivity and throughput is significant for the protection of food safety. In the present study, we coupled microarray with emulsion PCR and developed a high throughput detection method. Thirteen different gene sites which encode the common toxins of several bacteria and fungi were assayed in parallel in positive and maize samples. Conventional PCR assays were carried out for comparison. The results showed that the developed microarray method had high specificity and sensitivity. Two zearalenone-related genes were investigated in one of the ten maize samples obtained with this present method. The results indicated that the emulsion based microarray detection method was developed successfully and suggested its potential application in multiple gene site detection. Full article

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14 pages, 456 KiB

Open AccessArticle

A Practical Approach to New (5Z) 2-Alkylthio-5-arylmethylene-1-methyl-1,5-dihydro-4H-imidazol-4-one Derivatives

by Khadidja Bourahla¹, Ludovic Paquin¹, Olivier Lozach², Laurent Meijer², François Carreaux¹ and Jean Pierre Bazureau^1,*

¹ Chemical Engineering & Molecules for Life Sciences Group, Université de Rennes 1, Sciences Chimiques de Rennes (SCR), UMR CNRS 6226, Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes Cedex, France

² Protein Phosphorylation and Human Disease Group, Station Biologique CNRS, Place G. Tessier, BP 74, 29682 Roscoff, France

Molecules 2011, 16(9), 7377-7390; https://doi.org/10.3390/molecules16097377 - 30 Aug 2011

Cited by 9 | Viewed by 5772

Abstract

A practical protocol for the preparation of (5Z)-2-alkylthio-5-arylmethylene-1-methyl-1,5-dihydro-4H-imidazol-4-one derivatives is reported. The new compounds were obtained in good yield and stereoselectivity in two steps, namely a solvent-free Knoevenagel condensation under microwave irradiation, followed by an S-alkylation reaction with various halogenoalkanes. Full article

(This article belongs to the Section Organic Chemistry)

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10 pages, 381 KiB

Open AccessArticle

Microwave-Assisted Extraction of Oxymatrine from Sophora flavescens

by En-Qin Xia¹, Bo Cui¹, Xiang-Rong Xu², Yang Song¹, Xu-Xia Ai¹ and Hua-Bin Li^1,*

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China

² Key Laboratory of Marine Bio-resources Sustainable Utilization, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China

Molecules 2011, 16(9), 7391-7400; https://doi.org/10.3390/molecules16097391 - 30 Aug 2011

Cited by 26 | Viewed by 8058

Abstract

In this paper, microwave-assisted extraction (MAE) of oxymatrine from Sophora flavescens were studied by HPLC-photodiode array detection. Effects of several experimental parameters, such as concentration of extraction solvent, ratio of liquid to material, microwave power, extraction temperature, and extraction time on the extraction [...] Read more.

In this paper, microwave-assisted extraction (MAE) of oxymatrine from Sophora flavescens were studied by HPLC-photodiode array detection. Effects of several experimental parameters, such as concentration of extraction solvent, ratio of liquid to material, microwave power, extraction temperature, and extraction time on the extraction efficiencies of oxymatrine were evaluated. The optimal extraction conditions were 60% ethanol, a 20:1 (v/v) ratio of liquid to material and extraction for 10 min at 50 °C under 500 W microwave irradiation. Under the optimum conditions, the yield of oxymatrine was 14.37 mg/g. The crude extract obtained could be used as either a component of some complex traditional medicines or for further isolation and purification of bioactive compounds. The results, which indicated that MAE is a very useful tool for the extraction of important phytochemicals from plant materials, should prove helpful for the full utilization of Sophora flavescens. Full article

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14 pages, 503 KiB

Open AccessArticle

Antioxidant Capacity of Ocimum basilicum L. and Origanum vulgare L. Extracts

by Biljana Kaurinovic^*, Mira Popovic, Sanja Vlaisavljevic and Svetlana Trivic

Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, Trg Dositeja Obradovica 3, Novi Sad 21000, Serbia

Molecules 2011, 16(9), 7401-7414; https://doi.org/10.3390/molecules16097401 - 30 Aug 2011

Cited by 130 | Viewed by 11055

Abstract

The antioxidant properties of five different extracts (Et₂O, CHCl₃, EtOAc, n-BuOH, and H₂O) of Ocimum basilicum L. and Origanum vulgare L. were studied. Antioxidant activity was assessed in six different model systems. Free radical scavenging capacity [...] Read more.

The antioxidant properties of five different extracts (Et₂O, CHCl₃, EtOAc, n-BuOH, and H₂O) of Ocimum basilicum L. and Origanum vulgare L. were studied. Antioxidant activity was assessed in six different model systems. Free radical scavenging capacity (RSC) was evaluated by measuring the scavenging capacity of extracts on DPPH, NO, O₂^·- and OH radical, as well as on hydrogen peroxide (H₂O₂). In addition, the protective effects on lipid peroxidation in liposomes (LPx) were evaluated by TBA-assay using the Fe²⁺/ascorbate induction system. The amount of total phenolic compounds and content of total flavonoids was also determined. EtOAc, n-BuOH and H₂O extracts of O. basilicum and O. vulgare expressed very strong scavenger activity. Furthermore, the mentioned extracts showed notable inhibition of LPx. On the other hand, Et₂O and CHCl₃ extracts showed much weaker effect in the neutralization of DPPH, NO and O₂^·- radicals and the neutralization of H₂O₂. When examining the production of OH radicals and inhibition of LPx, the Et₂O and CHCl₃ extracts showed weak prooxidative properties. The observed differences in antioxidant activity could be partially explained by the levels of phenolics and flavonoids in the investigated O. basilicum and O. vulgare extracts. Full article

(This article belongs to the Special Issue Radical Chemistry)

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13 pages, 195 KiB

Open AccessArticle

Acute Toxicity and Hepatotoxicokinetic Studies of Tamarindus indica Extract

by Uchechukwu U. Nwodo^1,*, Augustine A. Ngene², Aruh O. Anaga³, Vincent N. Chigor¹, Igbinosa I. Henrietta¹ and Anthony I. Okoh¹

¹ Applied and Environmental Microbiology Research Group, Department of Biochemistry and Microbiology, University of Fort Hare, Private Bag 1314, Alice, 5700 Eastern Cape, South Africa

² Department of Veterinary Medicine, University of Nigeria, Nsukka, 410002, Enugu State, Nigeria

³ Department of Veterinary Physiology and Pharmacology, University of Nigeria, Nsukka, 410002, Enugu State, Nigeria

Molecules 2011, 16(9), 7415-7427; https://doi.org/10.3390/molecules16097415 - 31 Aug 2011

Cited by 10 | Viewed by 6941

Abstract

Tamarindus indica is widely used as a food and beverage and in traditional medicine. The apparent lack of dose standardization in herbal medicine necessitates the evaluation of the lethality T. indica on Artemia salina nauplii and chicken embryos via in vitro and [...] Read more.

Tamarindus indica is widely used as a food and beverage and in traditional medicine. The apparent lack of dose standardization in herbal medicine necessitates the evaluation of the lethality T. indica on Artemia salina nauplii and chicken embryos via in vitro and in vivo techniques. Furthermore, hepatotoxicokinetics of the crude extract and fractions on Wister rats was also assessed. At concentrations of 200, 20 and 2 µg/mL, crude extract and fractions showed brine shrimp death percentages ranging from 86.70% to 3.30% and the sub-fractions showed death percentage ranges of 46.70% to 3.30%. Calculated LD₅₀ values ranged from 832 µg/mL to 5,019 µg/mL. Dosing Wister rats with 25% and 50% concentration of LD₅₀ determined for crude extract and fractions on chicken embryos showed an elevation in the ALT and AST levels in the serum. Brine shrimps and chicken embryos showed a positive correlation, with R² values of 0.541 and 0.588 (P ≤ 0.05) for fractions and subfractions, respectively, as media for the lethality assay. Dose standardization in folk herbal medicine is imperative as T. indica used as food and medicine has been shown to be toxic at high doses. Brine shrimp and chicken embryos may be comparably used as medium for toxicity assay. Full article

30 pages, 3401 KiB

Open AccessArticle

Mathematical Evaluation of the Amino Acid and Polyphenol Content and Antioxidant Activities of Fruits from Different Apricot Cultivars

by Jiri Sochor¹, Helena Skutkova², Petr Babula¹, Ondrej Zitka¹, Natalia Cernei¹, Otakar Rop³, Boris Krska⁴, Vojtech Adam^1,5, Ivo Provazník² and Rene Kizek^1,5,*

¹ Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic

² Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Kolejni 4, CZ-612 00 Brno, Czech Republic

³ Department of Food Technology and Microbiology, Faculty of Technology, Tomas Bata University in Zlin, Namesti T. G. Masaryka 275, CZ-762 72 Zlin, Czech Republic

⁴ Department of Fruit Growing, Faculty of Horticulture, Mendel University in Brno, Valticka 337, CZ-691 44 Lednice, Czech Republic

⁵ Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czech Republic

Molecules 2011, 16(9), 7428-7457; https://doi.org/10.3390/molecules16097428 - 1 Sep 2011

Cited by 45 | Viewed by 8920

Abstract

Functional foods are of interest because of their significant effects on human health, which can be connected with the presence of some biologically important compounds. In this study, we carried out complex analysis of 239 apricot cultivars (Prunus armeniaca L.) cultivated in [...] Read more.

Functional foods are of interest because of their significant effects on human health, which can be connected with the presence of some biologically important compounds. In this study, we carried out complex analysis of 239 apricot cultivars (Prunus armeniaca L.) cultivated in Lednice (climatic area T4), South Moravia, Czech Republic. Almost all previously published studies have focused only on analysis of certain parameters. However, we focused on detection both primary and secondary metabolites in a selection of apricot cultivars with respect to their biological activity. The contents of thirteen biogenic alpha-L-amino acids (arginine, asparagine, isoleucine, lysine, serine, threonine, valine, leucine, phenylalanine, tryptophan, tyrosine, proline and alanine) were determined using ion exchange chromatography with UV-Vis spectrometry detection. Profile of polyphenols, measured as content of ten polyphenols with significant antioxidant properties (gallic acid, procatechinic acid, p-aminobenzoic acid, chlorogenic acid, caffeic acid, vanillin, p-coumaric acid, rutin, ferrulic acid and quercetrin), was determined by high performance liquid chromatography with spectrometric/electrochemical detection. Moreover, content of total phenolics was determined spectrophotometrically using the Folin-Ciocalteu method. Antioxidant activity was determined using five independent spectrophotometric methods: DPPH assay, DMPD method, ABTS method, FRAP and Free Radicals methods. Considering the complexity of the obtained data, they were processed and correlated using bioinformatics techniques (cluster analysis, principal component analysis). The studied apricot cultivars were clustered according to their common biochemical properties, which has not been done before. The observed similarities and differences were discussed. Full article

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22 pages, 616 KiB

Open AccessArticle

t-Bu₂SiF-Derivatized D₂-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging

by Ljuba Iovkova-Berends¹, Carmen Wängler², Thomas Zöller¹, Georg Höfner³, Klaus Theodor Wanner³, Christian Rensch⁴, Peter Bartenstein², Alexey Kostikov⁵, Ralf Schirrmacher⁵, Klaus Jurkschat^1,* and Björn Wängler^2,*

¹ Department of Inorganic Chemistry II, Faculty of Chemistry, TU Dortmund, Otto-Hahn-Str. 6, 44221 Dortmund, Germany

² Department of Nuclear Medicine, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany

³ Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University, Butenandtstr. 7, 81377 Munich, Germany

⁴ GE Global Research, 85748 Garching, Germany

⁵ McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University St., Montreal H3A 2B4, QC, Canada

Molecules 2011, 16(9), 7458-7479; https://doi.org/10.3390/molecules16097458 - 2 Sep 2011

Cited by 17 | Viewed by 9462

Abstract

The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D₂-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules [...] Read more.

The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D₂-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D₂-receptor affinities for all compounds in the nanomolar range (K_i(SiFA-DMFP) = 13.6 nM, K_i(SiFA-FP) = 33.0 nM, K_{i(SiFA-DDMFP)} = 62.7 nM and K_i(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with [¹⁸F]fluoride/TBAHCO₃ in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/µmol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

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8 pages, 544 KiB

Open AccessArticle

Application of Preparative High-Speed Counter-Current Chromatography for the Separation of Two Alkaloids from the Roots of Tabernaemontana catharinensis (Apocynaceae)

by Milena S. Gonçalves, Ivo J. Curcino Vieira^*, Rodrigo R. Oliveira and Raimundo Braz-Filho

Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602, Campos dos Goytacazes, Rio de Janeiro, Brazil

Molecules 2011, 16(9), 7480-7487; https://doi.org/10.3390/molecules16097480 - 2 Sep 2011

Cited by 10 | Viewed by 6379

Abstract

The methanolic extract of Tabernaemontana catharinensis (Apocynaceae) roots, which contains alkaloids with several biological activities, was separated on a preparative scale using high-speed counter-current chromatography. The optimum solvent system was found to be a mixture of CHCl₃-MeOH-H₂O [5:10:6 ( [...] Read more.

The methanolic extract of Tabernaemontana catharinensis (Apocynaceae) roots, which contains alkaloids with several biological activities, was separated on a preparative scale using high-speed counter-current chromatography. The optimum solvent system was found to be a mixture of CHCl₃-MeOH-H₂O [5:10:6 (v/v/v)] and led to a successful separation of two monoterpenic indole alkaloids, voachalotine (1) and 12-methoxy-N_b-methylvoachalotine (2) in approximately 4.0 hours. The alkaloids were all isolated at purities over 95%, and their structures were established on the basis of spectroscopic methods, including 1D and 2D NMR and EI/MS. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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14 pages, 412 KiB

Open AccessArticle

Thermal and Rheological Properties of a Family of Botryosphaerans Produced by Botryosphaeria rhodina MAMB-05

by Paulo R.M.S. Fonseca¹, Robert F.H. Dekker², Aneli M. Barbosa³, Joana L.M. Silveira⁴, Ana F.D. Vasconcelos¹, Nilson K. Monteiro¹, Gabriel Aranda-Selverio¹ and Maria de Lourdes Corradi Da Silva^1,*

¹ Department of Physics, Chemistry and Biology, Faculty of Science and Technology, University Estadual Paulista, Presidente Prudente 19060900, Brazil

² Biorefining Research Initiative, Lakehead University, Thunder Bay, ON, P7B 5E1, Canada

³ Department of Biochemistry and Biotechnology, CCE, State University of Londrina, Londrina 86051990, Brazil

⁴ Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba 81531990, Brazil

Molecules 2011, 16(9), 7488-7501; https://doi.org/10.3390/molecules16097488 - 2 Sep 2011

Cited by 14 | Viewed by 7058

Abstract

Differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier-transform infra-red spectroscopy (FT-IR) analyses were performed to investigate changes in the physico-chemical properties of botryosphaerans, a family of exopolysaccharides (EPS) produced by the fungus Botryosphaeria rhodina MAMB-05 grown on glucose (EPS_GLC), sucrose (EPS [...] Read more.

Differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier-transform infra-red spectroscopy (FT-IR) analyses were performed to investigate changes in the physico-chemical properties of botryosphaerans, a family of exopolysaccharides (EPS) produced by the fungus Botryosphaeria rhodina MAMB-05 grown on glucose (EPS_GLC), sucrose (EPS_SUC) and fructose (EPS_FRU). A slight endothermic transition and small mass loss attributable to the removal of water of hydration were observed in the DSC and TG analyses, respectively, for the three EPS samples. The FT-IR spectra confirmed no structural changes occurred during thermal treatment. Viscometry was utilized to obtain information on the rheological behaviour of the EPS in aqueous solutions. The Power Law and Cross Equations determined the natural pseudoplastic characteristics of the EPS. Comparatively, results obtained for EPS produced when B. rhodina MAMB-05 was grown on each of the three carbohydrate sources demonstrated similar apparent viscosity values for EPS_GLC and EPS_SUC, while EPS_FRU displayed the lowest apparent viscosity of the three botryosphaerans, suggesting a higher degree of ramification and lower Mw. EPS_GLC and EPS_SUC possessed similar degrees of ramification. The slight differences found in their viscosities can be explained by the differences in the type of branching among the three botryosphaerans, thus varying the strength of intermolecular interactions and consequently, consistency and viscosity. The physico-chemical studies of botryosphaerans represent the originality of this work, and the knowledge of these properties is an important criterion for potential applications. Full article

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8 pages, 354 KiB

Open AccessArticle

Bioactivity of Carica papaya (Caricaceae) against Spodoptera frugiperda (Lepidoptera: Noctuidae)

by Salud Pérez-Gutiérrez¹, Miguel Angel Zavala-Sánchez¹, Marco Martín González-Chávez², Norma Cecilia Cárdenas-Ortega² and Miguel Angel Ramos-López^1,*

¹ Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, México D.F. 04960, Mexico

² Centro de Investigación y Estudios de Posgrado, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, Zona Universitaria, San Luis Potosí, SLP, 78210, Mexico

Molecules 2011, 16(9), 7502-7509; https://doi.org/10.3390/molecules16097502 - 2 Sep 2011

Cited by 28 | Viewed by 8539

Abstract

The composition of a chloroform seed extract of C. papaya was determined by GC-MS. Nineteen compounds were identified, with oleic (45.97%), palmitic (24.1%) and stearic (8.52%) acids being the main components. The insecticidal and insectistatic activities of the extract and the three main [...] Read more.

The composition of a chloroform seed extract of C. papaya was determined by GC-MS. Nineteen compounds were identified, with oleic (45.97%), palmitic (24.1%) and stearic (8.52%) acids being the main components. The insecticidal and insectistatic activities of the extract and the three main constituents were tested. Larval duration increased by 3.4 d and 2.5 d when the extract was used at 16,000 and 9,600 ppm, respectively, whereas the pupal period increased by 2.2 d and 1.1 d at the same concentrations. Larval viability values were 0%, 29.2%, and 50% when the extract was applied at 24,000, 16,000, and 9,600 ppm, respectively; pupal viability was 42.9% and 66.7% at 16,000 and 9,600 ppm; and pupal weight decreased by 25.4% and 11.5% at 16,000 and 9,600 ppm. The larval viability of the main compounds was 33.3%, 48.5%, and 62.5% when exposed to 1,600 ppm of palmitic acid, oleic acid, or stearic acid, respectively. Full article

12 pages, 388 KiB

Open AccessArticle

Antioxidant, Anti-Lipoxygenase and Cytotoxic Activity of Leptadenia pyrotechnica (Forssk.) Decne Polyphenolic Constituents

by Mohammad A. Khasawneh^1,*

, Hanan M. Elwy^1,2, Alaaeldin A. Hamza³, Nael M. Fawzi³ and Ahmed H. Hassan⁴

¹ Department of Chemistry, Faculty of Science U.A.E. University, Al-Ain, P.O. Box 17551, UAE

² National Organization of Drug Control and Research, 6 Abu Hazem St., Giza, Egypt

³ Department of Biology, Faculty of Science U.A.E. University, Al-Ain, P.O. Box 17551, UAE

⁴ Department of Biochemistry, Faculty of Medicine and Health Sciences, U.A.E. University, Al-Ain, P.O. Box 17666, UAE

Molecules 2011, 16(9), 7510-7521; https://doi.org/10.3390/molecules16097510 - 5 Sep 2011

Cited by 40 | Viewed by 9702

Abstract

Leptadenia pyrotechnica Forssk is a traditional medicinal herb used for treatment of inflammatory diseases and cancer. In this research, the aqueous ethanolic crude extract of Leptadenia pyrotechnica aerial parts, along with its ethyl acetate, n-butanol and water partitioning fractions were evaluated for [...] Read more.

Leptadenia pyrotechnica Forssk is a traditional medicinal herb used for treatment of inflammatory diseases and cancer. In this research, the aqueous ethanolic crude extract of Leptadenia pyrotechnica aerial parts, along with its ethyl acetate, n-butanol and water partitioning fractions were evaluated for their antioxidant capacity, polyphenolic content, anti-inflammatory and anti-cancer properties. The total antioxidant capacity was estimated by the FRAP, DPPH, ABTS and β-carotene bleaching assays.The ethyl acetate fraction exhibited the highest polyphenolic content (252.27 mg gallic acid/g) and the best antioxidant activity (1.2, 0.57, 0.45 mmol ascorbic acid equivalent/g in the FRAP, ABTS and DPPH assays, respectively). Furthermore, the same extract showed appreciable anti-inflammatory via lipoxygenase (LOX) inhibitory activity (IC₅₀ = 1.41 µg/mL). Moreover, the ethyl acetate fraction also showed the strongest cytotoxic effect (IC₅₀ = 43.16 µg/mL) against MCF-7 human breast cancer cell line. These results suggest that this plant may be considered an interesting source of compounds with antioxidant, anti-inflammatory and anti-cancer properties for therapeutic, nutraceutical and functional food applications. Full article

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29 pages, 736 KiB

Open AccessReview

Recent Advances in Microflow Photochemistry

by Michael Oelgemöller^1,*

and Oksana Shvydkiv²

¹ School of Pharmacy and Molecular Sciences, James Cook University, Townsville, QLD 4811, Australia

² School of Chemical Sciences, Dublin City University, Dublin 9, Ireland

Molecules 2011, 16(9), 7522-7550; https://doi.org/10.3390/molecules16097522 - 5 Sep 2011

Cited by 170 | Viewed by 16736

Abstract

This review summarizes recent advances in microflow photochemical technologies and transformations. The portfolio of reactions comprises homogeneous and heterogeneous types, among them photoadditions, photorearrangements, photoreductions, photodecarboxylations, photooxygenations and photochlorinations. While microflow photochemistry is most commonly employed as a micro-scale synthesis tool, scale-up and [...] Read more.

This review summarizes recent advances in microflow photochemical technologies and transformations. The portfolio of reactions comprises homogeneous and heterogeneous types, among them photoadditions, photorearrangements, photoreductions, photodecarboxylations, photooxygenations and photochlorinations. While microflow photochemistry is most commonly employed as a micro-scale synthesis tool, scale-up and technical production processes have already been developed. Full article

(This article belongs to the Special Issue Flow Chemistry)

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14 pages, 557 KiB

Open AccessArticle

Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome

by Yuheng Ma, Bo Xu, Yuan Fang, Zhenjun Yang, Jingrong Cui, Liangren Zhang^* and Lihe Zhang

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

Molecules 2011, 16(9), 7551-7564; https://doi.org/10.3390/molecules16097551 - 5 Sep 2011

Cited by 18 | Viewed by 7594

Abstract

Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), [...] Read more.

Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(OBzl)-Leu-Leucinal (3o) exhibited the most activity, which represented an order of magnitude enhancement compared with MG132 (2). The covalent docking protocol was used to explore the binding mode. The structure-activity relationship of the peptide aldehyde inhibitors is discussed. Full article

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18 pages, 756 KiB

Open AccessArticle

1,3-Substituted Imidazolidine-2,4,5-triones: Synthesis and Inhibition of Cholinergic Enzymes

by Vladimir Pejchal¹, Sarka Stepankova²

, Zdenka Padelkova³, Ales Imramovsky^1,* and Josef Jampilek^4,*

¹ Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic

² Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 53210, Czech Republic

³ Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic

⁴ Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic

Molecules 2011, 16(9), 7565-7582; https://doi.org/10.3390/molecules16097565 - 5 Sep 2011

Cited by 25 | Viewed by 6553

Abstract

A series of novel and highly active acetylcholinesterase and butyrylcholinesterase inhibitors derived from substituted benzothiazoles containing an imidazolidine-2,4,5-trione moiety were synthesized and characterized. The molecular structure of 1-(2,6-diisopropyl-phenyl)-3-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-imidazolidine-2,4,5-trione (3g) was determined by single-crystal X-ray diffraction. Both optical isomers are [...] Read more.

A series of novel and highly active acetylcholinesterase and butyrylcholinesterase inhibitors derived from substituted benzothiazoles containing an imidazolidine-2,4,5-trione moiety were synthesized and characterized. The molecular structure of 1-(2,6-diisopropyl-phenyl)-3-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-imidazolidine-2,4,5-trione (3g) was determined by single-crystal X-ray diffraction. Both optical isomers are present as two independent molecules in the triclinic crystal system. The lipophilicity of the compounds was determined as the partition coefficient log K_ow using the traditional shake-flask method. The in vitro inhibitory activity on acetylcholinesterase from electric eel and butyrylcholinesterase isolated from equine serum was determined. The inhibitory activity on acetylcholinesterase was significantly higher than that of the standard drug rivastigmine. The discussed compounds are also promising inhibitors of butyrylcholinesterase, as some of the prepared compounds inhibit butyrylcholinesterase better than the internal standards rivastigmine and galanthamine. The highest inhibitory activity (IC₅₀ = 1.66 μmol/L) corresponds to the compound 1-(4-isopropylphenyl)-3-[(R)-1-(6-fluorobenzo[d]thiazol-2-yl)ethyl]imidazolidine-2,4,5-trione (3d). For all the studied compounds, the relationships between the lipophilicity and the chemical structure as well as their structure-activity relationships are discussed. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 797 KiB

Open AccessArticle

Bioassay-Directed Isolation of Active Compounds with Antiyeast Activity from a Cassia fistula Seed Extract

by Subramanion L. Jothy¹, Zuraini Zakaria¹, Yeng Chen^2,3,*, Yee Ling Lau⁴, Lachimanan Yoga Latha², Lai Ngit Shin² and Sreenivasan Sasidharan²

¹ Biological Program, School of Distance Education, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia

² Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang, Malaysia

³ Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia

⁴ Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

Molecules 2011, 16(9), 7583-7592; https://doi.org/10.3390/molecules16097583 - 5 Sep 2011

Cited by 34 | Viewed by 9024

Abstract

Background and objective: Cassia fistula L belongs to the family Leguminosae, and it is one of the most popular herbal products in tropical countries. C. fistula seeds have been used as a herbal medicine and have pharmacological activity which includes anti-bacterial, anti-fungal, [...] Read more.

Background and objective: Cassia fistula L belongs to the family Leguminosae, and it is one of the most popular herbal products in tropical countries. C. fistula seeds have been used as a herbal medicine and have pharmacological activity which includes anti-bacterial, anti-fungal, and antioxidant properties. The goal of this study was to identify compounds from C. fistula seeds which are responsible for anti-Candida albicans activity using bioassay-directed isolation. Results: The preliminary phytochemical screening of the plant seed revealed the presence of anthraquinones, flavonoids, saponins, tannins and terpenoids. The isolation of active compounds was carried out in four steps: multiple extractions, fractionation using column chromatography and purification using preparative thin-layer chromatography (TLC) and liquid chromatography/mass spectrometry (LC/MS). The structure of separated compounds was determined on the basis of mass spectrometry data. One compound was identified is roseanone. Conclusions: The MS analysis on the active fraction from seed extract of C. fistula confirmed the presence of roseanone with antiyeast activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 453 KiB

Open AccessArticle

Synthesis, Spectroscopic Properties and Antipathogenic Activity of New Thiourea Derivatives

by Carmen Limban¹, Luminita Marutescu² and Mariana Carmen Chifiriuc^2,3,*

¹ Pharmaceutical Chemistry Department, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania

² Microbiology Department, Faculty of Biology, University of Bucharest, Ale. Portocalelor 1-4, Bucharest 60101, Romania

³ National Institute for Research and Development in Microbiology and Immunology “Cantacuzino”, Spl. Independentei 103, Bucharest 060031, Romania

Molecules 2011, 16(9), 7593-7607; https://doi.org/10.3390/molecules16097593 - 6 Sep 2011

Cited by 69 | Viewed by 7268

Abstract

A number of acylthioureas, 2-((4-methylphenoxy)methyl)-N-(aryl-carbamothioyl)benzamides (aryl = 3,5-dichlorophenyl, 2,3-dichlorophenyl, 3,4-dichloro-phenyl, 2,4,5-trichlorophenyl, 3,4,5-trichlorophenyl, 2-bromophenyl, 2,4-dibromophenyl, 2,5-dibromophenyl, 2-iodophenyl, 3-fluorophenyl, 2,3,4-trifluorophenyl, 2,4,5-trifluoro-phenyl, 2,4,6-trifluorophenyl) have been synthesized, characterized by elemental analysis, IR and NMR spectroscopy and tested for their interaction with bacterial cells in free [...] Read more.

A number of acylthioureas, 2-((4-methylphenoxy)methyl)-N-(aryl-carbamothioyl)benzamides (aryl = 3,5-dichlorophenyl, 2,3-dichlorophenyl, 3,4-dichloro-phenyl, 2,4,5-trichlorophenyl, 3,4,5-trichlorophenyl, 2-bromophenyl, 2,4-dibromophenyl, 2,5-dibromophenyl, 2-iodophenyl, 3-fluorophenyl, 2,3,4-trifluorophenyl, 2,4,5-trifluoro-phenyl, 2,4,6-trifluorophenyl) have been synthesized, characterized by elemental analysis, IR and NMR spectroscopy and tested for their interaction with bacterial cells in free and adherent state. The anti-pathogenic activity was correlated with the presence of one iodine, bromide or fluorine, and two or three chloride atoms on the N-phenyl substituent of the thiourea moiety, being significant especially on Pseudomonas aeruginosa and Staphylococcus aureus strains, known for their ability to grow in biofilms. Our results demonstrate the potential of these derivatives for further development of novel anti-microbial agents with antibiofilm properties. Full article

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13 pages, 1295 KiB

Open AccessArticle

Studies on the Electrochemical Behavior of Thiazolidine and Its Applications Using a Flow–Through Chronoamperometric Sensor Based on a Gold Electrode

by Lai-Hao Wang^* and Wen-Jie Li

Department of Medical Chemistry, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road, Section 1, Jen Te, Tainan 71743, Taiwan

Molecules 2011, 16(9), 7608-7620; https://doi.org/10.3390/molecules16097608 - 6 Sep 2011

Cited by 1 | Viewed by 5621

Abstract

The electrochemical behaviors of thiazolidine (tetrahydrothiazole) on gold and platinum electrodes were investigated in a Britton-Robinson buffer (pH 2.77–11.61), acetate buffer (pH 4.31), phosphate buffer solutions (pH 2.11 and 6.38) and methanol or acetonitrile containing various supporting electrolytes. Detection was based on a [...] Read more.

The electrochemical behaviors of thiazolidine (tetrahydrothiazole) on gold and platinum electrodes were investigated in a Britton-Robinson buffer (pH 2.77–11.61), acetate buffer (pH 4.31), phosphate buffer solutions (pH 2.11 and 6.38) and methanol or acetonitrile containing various supporting electrolytes. Detection was based on a gold wire electrochemical signal obtained with a supporting electrolyte containing 20% methanol-1.0 mM of phosphate buffer (pH 6.87, potassium dihydrogen phosphate and dipotassium hydrogen phosphate) as the mobile phase. Comparison with results obtained with a commercial amperometric detector shows good agreement. Using the chronoamperometric sensor with the current at a constant potential, and measurements with suitable experimental parameters, a linear concentration from 0.05 to 16 mg L⁻¹ was found. The limit of quantification (LOQ) of the method for thiazolidine was found to be 1 ng. Full article

(This article belongs to the Special Issue Gold Catalysts)

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6 pages, 402 KiB

Open AccessCommunication

Synthesis of No-Carrier-Added 4-[¹⁸F]Fluorophenol from 4-Benzyloxyphenyl-(2-thienyl)iodonium Bromide

by Tobias L. Ross^†, Johannes Ermert^*

and Heinz H. Coenen

¹ Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

^† Current address: Institute of Nuclear Chemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany.

Molecules 2011, 16(9), 7621-7626; https://doi.org/10.3390/molecules16097621 - 6 Sep 2011

Cited by 15 | Viewed by 5617

Abstract

4-[¹⁸F]Fluorophenol is a versatile synthon for the synthesis of more complex radiopharmaceuticals bearing a 4-[¹⁸F]fluorophenoxy moiety. In order to prepare 4-[¹⁸F]fluorophenol in no-carrier-added (n.c.a.) form only a nucleophilic labelling method starting from [¹⁸F]fluoride is suitable. [...] Read more.

4-[¹⁸F]Fluorophenol is a versatile synthon for the synthesis of more complex radiopharmaceuticals bearing a 4-[¹⁸F]fluorophenoxy moiety. In order to prepare 4-[¹⁸F]fluorophenol in no-carrier-added (n.c.a.) form only a nucleophilic labelling method starting from [¹⁸F]fluoride is suitable. In this paper a new, two step radiosynthesis starting from 4-benzyloxyphenyl-(2-thienyl)iodonium bromide and [¹⁸F]fluoride with subsequent deprotection is described, yielding n.c.a. [¹⁸F]fluorophenol in 34 to 36% radiochemical yield. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

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7 pages, 484 KiB

Open AccessCommunication

Synthesis and Structural Characterization of 1-[2-(5-Nitro-1H-indol-2-yl)phenyl]methylpyridinium Chloride

by John B. Bremner^1,*, Siritron Samosorn², Brian W. Skelton³ and Allan H. White³

¹ School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia

² Department of Chemistry, Srinakharinwirot University, Bangkok 10110, Thailand

³ School of Biomedical, Biomolecular and Chemical Sciences, Chemistry M313, The University of Western Australia, Crawley, W.A. 6009, Australia

Molecules 2011, 16(9), 7627-7633; https://doi.org/10.3390/molecules16097627 - 6 Sep 2011

Cited by 2 | Viewed by 5397

Abstract

In the course of studies on hybrid antibacterials incorporating 2-aryl-5-nitro-1H-indole moieties as potential bacterial NorA efflux pump inhibitors, the compound 1-[2-(5-nitro-1H-indol-2-yl)phenyl]methylpyridinium chloride (2) was synthesized and structurally characterized. This pyridinium chloride salt crystallized in the monoclinic space [...] Read more.

In the course of studies on hybrid antibacterials incorporating 2-aryl-5-nitro-1H-indole moieties as potential bacterial NorA efflux pump inhibitors, the compound 1-[2-(5-nitro-1H-indol-2-yl)phenyl]methylpyridinium chloride (2) was synthesized and structurally characterized. This pyridinium chloride salt crystallized in the monoclinic space group P2₁/c with the following unit cell dimensions: a 10.274(3) Å, b 13.101(4) Å, c 13.439(4) Å, b 107.702(7)°, V 1723.2(9) Å3, Z (f.u.) = 4; R1 = 0.048, and wR2 = 0.13. Of interest in the single crystal X-ray structure is the (intramolecular) disposition of the pyridinium plane over the indole heterocyclic residue [interplanar dihedral angle 17.91(4)°]. Full article

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15 pages, 1061 KiB

Open AccessArticle

A Novel Anti-Inflammatory Role for Ginkgolide B in Asthma via Inhibition of the ERK/MAPK Signaling Pathway

by Xiao Chu^1,†, Xinxin Ci^1,†, Jiakang He^2,†, Miaomiao Wei¹, Xiaofeng Yang¹, Qingjun Cao³, Hongyu Li¹, Shuang Guan¹, Yanhong Deng¹, Daxin Pang^4,* and Xuming Deng^1,*

¹ Key Laboratory of Zoonosis Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China

² College of Animal Science and Technology, Guangxi University, 100 Daxue Road, Nanning 530005, Guangxi, China

³ College of Plant Science, Jilin University, Changchun 130062, China

⁴ Key Laboratory of Animal Embryo Engineering, Department of Animal Biotechnology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China

^† These authors contributed equally to this work.

Molecules 2011, 16(9), 7634-7648; https://doi.org/10.3390/molecules16097634 - 6 Sep 2011

Cited by 67 | Viewed by 9804

Abstract

Ginkgolide B is an anti-inflammatory extract of Ginkgo biloba and has been used therapeutically. It is a known inhibitor of platelet activating factor (PAF), which is important in the pathogenesis of asthma. Here, a non-infectious mouse model of asthma is used to evaluate [...] Read more.

Ginkgolide B is an anti-inflammatory extract of Ginkgo biloba and has been used therapeutically. It is a known inhibitor of platelet activating factor (PAF), which is important in the pathogenesis of asthma. Here, a non-infectious mouse model of asthma is used to evaluate the anti-inflammatory capacity of ginkgolide B (GKB) and characterize the interaction of GKB with the mitogen activated protein kinase (MAPK) pathway. BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with GKB (40 mg/kg) one hour before they were challenged with OVA. Our study demonstrated that GKB may effectively inhibit the increase of T-helper 2 cytokines, such as interleukin (IL)-5 and IL-13 in bronchoalveolar lavage fluid (BALF). Furthermore, the eosinophil count in BALF significantly decreased after treatment of GKB when compared with the OVA-challenged group. Histological studies demonstrated that GKB substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. These results suggest that ginkgolide B may be useful for the treatment of asthma and its efficacy is related to suppression of extracellular regulating kinase/MAPK pathway. Full article

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13 pages, 592 KiB

Open AccessArticle

Synthesis of Quinolin-2-one Alkaloid Derivatives and Their Inhibitory Activities against HIV-1 Reverse Transcriptase

by Pi Cheng^1,3,*, Qiong Gu², Wei Liu¹, Jian-Feng Zou¹, Yang-Yong Ou³, Zhong-Yong Luo³ and Jian-Guo Zeng^1,3,*

¹ National Research Center of Engineering Technology For Utilization of Functional Ingredients From Botanicals, College of Horticulture and Landscape Architecture, Hunan Agricultural University, Changsha 410128, Hunan, China

² School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong,China

³ Hunan Engineering Research Center of Botanical Extract, Changsha410128, Hunan, China

Molecules 2011, 16(9), 7649-7661; https://doi.org/10.3390/molecules16097649 - 7 Sep 2011

Cited by 26 | Viewed by 9854

Abstract

Based on an established common pharmacophore of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNTTIs), a series of quinolin-2-one derivatives were synthesized and assayed for their in vitro activities against HIV-1 reverse transcriptase (RT) for the first time. Some of the tested compounds were active [...] Read more.

Based on an established common pharmacophore of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNTTIs), a series of quinolin-2-one derivatives were synthesized and assayed for their in vitro activities against HIV-1 reverse transcriptase (RT) for the first time. Some of the tested compounds were active against HIV-1 RT. Compounds 4a2 and 4d2 showed inhibitory activities with IC₅₀ values of 0.21 and 0.15 mM, respectively, with a mode of interaction with RT residues of the allosteric pocket similar to that of efavirenz. Full article

(This article belongs to the Special Issue Antivirals)

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10 pages, 462 KiB

Open AccessArticle

Synthesis of Some Oxadiazole Derivatives as New Anticandidal Agents

by Zafer Asim Kaplancikli

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

Molecules 2011, 16(9), 7662-7671; https://doi.org/10.3390/molecules16097662 - 7 Sep 2011

Cited by 24 | Viewed by 6300

Abstract

In this study, 5-[(pyrimidin-2-ylthio)methyl]-1,3,4-oxadiazole-2(3H)-thione (3) was synthesized via the ring closure reaction of 2-(pyrimidin-2-ylthio)acetohydrazide (2) with carbon disulphide. New oxadiazole derivatives 4a-f were obtained by the nucleophilic substitution reaction of compound 3 with various phenacyl bromides. The chemical structures [...] Read more.

In this study, 5-[(pyrimidin-2-ylthio)methyl]-1,3,4-oxadiazole-2(3H)-thione (3) was synthesized via the ring closure reaction of 2-(pyrimidin-2-ylthio)acetohydrazide (2) with carbon disulphide. New oxadiazole derivatives 4a-f were obtained by the nucleophilic substitution reaction of compound 3 with various phenacyl bromides. The chemical structures of the compounds were elucidated by IR, ¹H-NMR, ¹³C-NMR and FAB⁺-MS spectral data and elemental analyses. The newly synthesized derivatives 4a-f were tested in vitro by using a microbroth dilution method against C. albicans (clinical isolate, Osmangazi University, Faculty of Medicine, Eskişehir, Turkey), C. albicans (ATCC 90028), C. glabrata (clinical isolate, Osmangazi University, Faculty of Medicine, Eskişehir, Turkey), C. tropicalis (NRRL Y-12968), C. krusei (NRRL Y-7179), C. parapsilosis (NRRL Y- 12696), C. albicans (NRRL Y-12983), C. glabrata (clinical isolate, Anadolu University, Faculty of Science, Department of Biology, Eskişehir, Turkey). Among these compounds, compound 4a was found to be the most potent derivative (MIC = 0.007–0.06 versus ketoconazole: 0.001–0.007 mg/mL) against Candida species, except C. tropicalis and C. krusei when compared with the standard antifungal ketoconazole. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 493 KiB

Open AccessArticle

Antioxidant and Antiacetylcholinesterase Activities of Some Commercial Essential Oils and Their Major Compounds

by Smail Aazza^1,2, Badiâ Lyoussi¹ and Maria G. Miguel^2,*

¹ Laboratory of Physiology-Pharmacology-Environmental Health, Faculty of Sciences Dhar El Mehraz, BP 1796 Atlas, University Sidi Mohamed Ben Abdallah, Fez 30 000, Morocco

² Plant Biotechnology Research Group, Department of Chemistry and Pharmacy, Institute for Biotechnology and Bioengineering, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal

Molecules 2011, 16(9), 7672-7690; https://doi.org/10.3390/molecules16097672 - 7 Sep 2011

Cited by 228 | Viewed by 15975

Abstract

The commercial essential oils of Citrus aurantium L., Cupressus sempervirens L., Eucalyptus globulus Labill., Foeniculum vulgare Mill. and Thymus vulgaris L., isolated by steam distillation by a company of Morocco were evaluated in terms of in vitro antioxidant activity through several methods. In [...] Read more.

The commercial essential oils of Citrus aurantium L., Cupressus sempervirens L., Eucalyptus globulus Labill., Foeniculum vulgare Mill. and Thymus vulgaris L., isolated by steam distillation by a company of Morocco were evaluated in terms of in vitro antioxidant activity through several methods. In vitro acetylcholinesterase inhibitory activity was also determined. Citrus limon (L.) Burm. f. oil was also studied, but it was obtained by peel expression. The best antioxidant was T. vulgaris oil, independent of the method used, mainly due to the presence of the phenolic monoterpenes thymol and carvacrol, which when studied as single compounds also presented the best activities. Concerning the acetylcholinesterase inhibition activity, E. globulus was the most effective. Nevertheless its main components 1,8-cineole and limonene were not the most active, a feature that corresponded to d-3-carene. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 454 KiB

Open AccessArticle

Synthesis and Transformations of di-endo-3-Aminobicyclo-[2.2.2]oct-5-ene-2-carboxylic Acid Derivatives

by Márta Palkó¹, Pál Sohár² and Ferenc Fülöp^1,*

¹ Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary

² Institute of Chemistry, Eötvös Lóránd University, H-1518 Budapest, POB 32, Hungary

Molecules 2011, 16(9), 7691-7705; https://doi.org/10.3390/molecules16097691 - 7 Sep 2011

Cited by 12 | Viewed by 7671

Abstract

all-endo-3-amino-5-hydroxybicyclo[2.2.2]octane-2-carboxylic acid (13) and all-endo-5-amino-6-(hydroxymethyl)bicyclo[2.2.2]octan-2-ol (10) were prepared via dihydro-1,3-oxazine or g-lactone intermediates by the stereoselective functionalization of an N-protected derivative of endo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid (2). Ring closure of b-amino ester [...] Read more.

all-endo-3-amino-5-hydroxybicyclo[2.2.2]octane-2-carboxylic acid (13) and all-endo-5-amino-6-(hydroxymethyl)bicyclo[2.2.2]octan-2-ol (10) were prepared via dihydro-1,3-oxazine or g-lactone intermediates by the stereoselective functionalization of an N-protected derivative of endo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid (2). Ring closure of b-amino ester 4 resulted in tricyclic pyrimidinones 15 and 16. The structures, stereochemistry and relative configurations of the synthesized compounds were determined by IR and NMR. Full article

(This article belongs to the Section Molecular Diversity)

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9 pages, 478 KiB

Open AccessArticle

Synthesis and Chemical Characterisation of Some New Diheteroaryl Thienothiophene Derivatives

by Yahia Nasser Mabkhot^*

, Abdullah Mohammad Al-Majid and Abdullah S. Alamary

Department of Chemistry, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2011, 16(9), 7706-7714; https://doi.org/10.3390/molecules16097706 - 8 Sep 2011

Cited by 18 | Viewed by 5782

Abstract

Treatment of 1-(5-acetyl-3,4-dimethythieno[2,3-b]thiophene-2yl)ethanone (1) with dimethylformamide dimethyl acetal afforded enaminone derivative 2, which reacted with amino derivatives to give the corresponding bis-pyrimidine, bis-pyrazole, bis-triazolo-pyrimidine and bis-benzoimidazopyrimidine derivatives. Full article

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10 pages, 604 KiB

Open AccessArticle

Crystal Structure and Density Functional Theory Study on Structural Properties and Energies of a Isonicotinohydrazide Compound

by Hajar Sahebalzamani¹, Nina Khaligh¹, Shahriar Ghammamy^2,*, Farshid Salimi¹ and Kheyrollah Mehrani¹

¹ Department of Chemistry, Faculty of Science, Ardabil Branch, Islamic Azad University, Ardabil, Iran

² Department of Chemistry, Facutly of Science, Takestan Branch, Islamic Azad University, Takestan, Iran

Molecules 2011, 16(9), 7715-7724; https://doi.org/10.3390/molecules16097715 - 8 Sep 2011

Cited by 19 | Viewed by 5825

Abstract

An X-ray and a theoretical study of the structure of the isoniazid derivative N'-(4-dimethylaminobenzylidene)-isonicotinohydrazide monohydrate (1) are reported. In this work, we will report a combined experimental and theoretical study on the molecular structure, vibrational spectra and energies of N' [...] Read more.

An X-ray and a theoretical study of the structure of the isoniazid derivative N'-(4-dimethylaminobenzylidene)-isonicotinohydrazide monohydrate (1) are reported. In this work, we will report a combined experimental and theoretical study on the molecular structure, vibrational spectra and energies of N'-(4-dimethylaminobenzylidene)-isonicotinohydrazide monohydrate. The calculated parameters are in good agreement with the corresponding X-ray diffraction values. The FTIR spectrum in the range of 400–4000 cm⁻¹ of N'-(4-dimethylaminobenzylidene)-isonicotinohydrazide monohydrate has been recorded. The molecular geometry and vibrational frequencies and energies in the ground state are calculated by using the DFT (B3LYP, PBE1PBE) methods with 6-311G** basis sets. The calculated HOMO and LUMO energies also confirm that charge transfer occurs within the molecule. The geometries and normal modes of vibrations obtained from B3LYP/PBE1PBE/6-311G** calculations are in good agreement with the experimentally observed data. Full article

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11 pages, 317 KiB

Open AccessArticle

Chemical Composition and Possible in Vitro Phytotoxic Activity of Helichrsyum italicum (Roth) Don ssp. italicum

by Emilia Mancini¹, Laura De Martino¹

, Aurelio Marandino¹, Maria Rosa Scognamiglio² and Vincenzo De Feo^1,*

¹ Dipartimento di Scienze Farmaceutiche e Biomediche, Università degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano (Salerno), Italy

² Dipartimento di Ingegneria Industriale, Università degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano (Salerno), Italy

Molecules 2011, 16(9), 7725-7735; https://doi.org/10.3390/molecules16097725 - 8 Sep 2011

Cited by 46 | Viewed by 8637

Abstract

The chemical composition of the essential oil of Helichrysum italicum (Roth) Don ssp. italicum, collected in the National Park of Cilento and Diano Valley, Southern Italy, was studied by means of GC and GC/MS. Forty four compounds of 45 constituents were [...] Read more.

The chemical composition of the essential oil of Helichrysum italicum (Roth) Don ssp. italicum, collected in the National Park of Cilento and Diano Valley, Southern Italy, was studied by means of GC and GC/MS. Forty four compounds of 45 constituents were identified in the oil, mainly oxygenated sesquiterpenes. The essential oil was evaluated for its potential in vitro phytotoxic activity against germination and early radicle elongation of radish and garden cress. The radicle elongation of radish was significantly inhibited at the highest doses tested, while germination of both seeds was not affected. Full article

10 pages, 430 KiB

Open AccessArticle

Synthesis and in Vitro Antimicrobial Activity of Some Pyrazolyl-1-carboxamide Derivatives

by Essam Mohamed Sharshira^1,* and Nagwa Mohamed Mahrous Hamada²

¹ Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 426, Egypt

² Department of Chemistry, Faculty of Education, Alexandria University, Alexandria 21526, Egypt

Molecules 2011, 16(9), 7736-7745; https://doi.org/10.3390/molecules16097736 - 9 Sep 2011

Cited by 40 | Viewed by 7012

Abstract

A series of 3,5-disubstituted pyrazole-1-carboxamides were obtained by treatment of chalcones with semicarbazide hydrochloride in dioxane containing sodium acetate/acetic acid as a buffer solution. N-acetyl derivatives of pyrazole-1-carboxamides were isolated in good yields either by treatment of the carboxamide derivatives with acetic anhydride [...] Read more.

A series of 3,5-disubstituted pyrazole-1-carboxamides were obtained by treatment of chalcones with semicarbazide hydrochloride in dioxane containing sodium acetate/acetic acid as a buffer solution. N-acetyl derivatives of pyrazole-1-carboxamides were isolated in good yields either by treatment of the carboxamide derivatives with acetic anhydride or refluxing chalcones with semicarbazide in ethanol containing few drops of acetic acid to give the corresponding hydrazones. Subsequent treatment of hydrazones with acetic anhydride gave the desired N-acetyl pyrazole-1-carboxamides derivatives. When chalcones were refluxed with dioxane containing few drops of acetic acid, 4,5-dihydropyrazole-1-carboxamides were isolated, which were subsequently oxidized using 5% sodium hypochlorite in dioxane to afford pyrazole-1-carboxamides. The structures of isolated compounds were confirmed by elemental analyses and spectral methods. The isolated compounds were tested for their antimicrobial activities. Full article

(This article belongs to the Special Issue Heterocycles)

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16 pages, 535 KiB

Open AccessArticle

Stopped-Flow Spectrophotometric Study of the Kinetics and Mechanism of CO₂ Uptake by cis-[Cr(C₂O₄)(BaraNH₂)(OH₂)₂]⁺ Cation and the Acid-Catalyzed Decomposition of cis-[Cr(C₂O₄)(BaraNH₂)OCO₂]⁻ Anion in Aqueous Solution

by Dagmara Jacewicz^*, Aleksandra Dąbrowska and Lech Chmurzyński

Department of General and Inorganic Chemistry, University of Gdańsk, Sobieskiego 18/19, 80-952 Gdańsk, Poland

Molecules 2011, 16(9), 7746-7761; https://doi.org/10.3390/molecules16097746 - 9 Sep 2011

Cited by 5 | Viewed by 6693

Abstract

The kinetics of CO₂ uptake by the cis-[Cr(C₂O₄)(BaraNH₂)(OH₂)₂]⁺ complex cation and the acid hydrolysis of the cis-[Cr(C₂O₄)(BaraNH₂)OCO₂]⁻ complex anion (where [...] Read more.

The kinetics of CO₂ uptake by the cis-[Cr(C₂O₄)(BaraNH₂)(OH₂)₂]⁺ complex cation and the acid hydrolysis of the cis-[Cr(C₂O₄)(BaraNH₂)OCO₂]⁻ complex anion (where BaraNH₂ denotes methyl 3-amino-2,3-dideoxy-b-D-arabino-hexopyranoside) were studied using the stopped-flow technique. The reactions under study were investigated in aqueous solution in the 288–308 K temperature range. In the case of the reaction between CO₂ and cis-[Cr(C₂O₄)(BaraNH₂)(OH₂)₂]⁺ cation variable pH values (6.82–8.91) and the constant ionic strength of solution (H⁺, Na⁺, ClO₄⁻ = 1.0) were used. Carbon dioxide was generated by the reaction between sodium pyruvate and hydrogen peroxide. The acid hydrolysis of cis-[Cr(C₂O₄)(BaraNH₂)OCO₂]⁻ was investigated for varying concentrations of H⁺ ions (0.01–2.7 M). The obtained results enabled the determination of the number of steps of the studied reactions. Based on the kinetic equations, rate constants were determined for each step. Finally, mechanisms for both reactions were proposed and discussed. Based on the obtained results it was concluded that the carboxylation (CO₂ uptake) reactions of cis-[Cr(C₂O₄)(BaraNH₂)(OH₂)₂]⁺ and the decarboxylation (acid hydrolysis) of the cis-[Cr(C₂O₄)(BaraNH₂)OCO₂]⁻ are the opposite of each other. Full article

(This article belongs to the Special Issue Flow Chemistry)

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11 pages, 266 KiB

Open AccessArticle

Physicochemical Properties, in Vitro Antioxidant Activities and Inhibitory Potential against α-Glucosidase of Polysaccharides from Ampelopsis grossedentata Leaves and Stems

by Yuefei Wang, Xiaoying Bian, Jinhyouch Park, Le Ying, Lisheng Qian and Ping Xu^*

Department of Tea Science, Zhejiang University, Hangzhou 310058, China

Molecules 2011, 16(9), 7762-7772; https://doi.org/10.3390/molecules16097762 - 9 Sep 2011

Cited by 28 | Viewed by 6831

Abstract

In the present study, polysaccharides named ALPS and ASPS were isolated from Ampelopsis grossedentata leaves and stems, respectively. Physicochemical properties, in vitro antioxidant activities and the inhibitory effects on α-glucosidase of ALPS and ASPS were investigated. It was found that both ALPS and [...] Read more.

In the present study, polysaccharides named ALPS and ASPS were isolated from Ampelopsis grossedentata leaves and stems, respectively. Physicochemical properties, in vitro antioxidant activities and the inhibitory effects on α-glucosidase of ALPS and ASPS were investigated. It was found that both ALPS and ASPS were acid protein-bound heteropolysaccharides, although with considerably different chemical composition and molecular weight distribution. Meanwhile, in comparison with ALPS, ASPS exhibited stronger antioxidant activity and inhibitory potential against α-glucosidase according to the in vitro evaluation. Moreover, our results suggested that protein and uronic acid might, at least partly, contribute positively to the biological behavior of ALPS and ASPS. Full article

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16 pages, 448 KiB

Open AccessArticle

Chemical, Antioxidant and Antimicrobial Investigations of Pinus cembra L. Bark and Needles

by Cristina Lungu Apetrei¹, Cristina Tuchilus², Ana Clara Aprotosoaie³, Adrian Oprea⁴, Karl Egil Malterud⁵ and Anca Miron^3,*

¹ Department of Plant and Animal Biology, School of Pharmacy, Gr. T. Popa University of Medicine and Pharmacy, Universitatii Street Number 16, 700115 Iasi, Romania

² Department of Microbiology, School of Medicine, Gr. T. Popa University of Medicine and Pharmacy, Universitatii Street Number 16, 700115 Iasi, Romania

³ Department of Pharmacognosy, School of Pharmacy, Gr. T. Popa University of Medicine and Pharmacy, Universitatii Street Number 16, 700115 Iasi, Romania

⁴ Institute of Biological Research, Lascar Catargi Street Number 47, 700107 Iasi, Romania

⁵ Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. 1068, Blindern, 0316 Oslo, Norway

Molecules 2011, 16(9), 7773-7788; https://doi.org/10.3390/molecules16097773 - 13 Sep 2011

Cited by 84 | Viewed by 12886

Abstract

The chemical constituents and biological activity of Pinus cembra L. (Pinaceae), native to the Central European Alps and the Carpathian Mountains, are not well known. The aim of the present work was to examine the phenolic content, antioxidant and antimicrobial effects of hydromethanolic [...] Read more.

The chemical constituents and biological activity of Pinus cembra L. (Pinaceae), native to the Central European Alps and the Carpathian Mountains, are not well known. The aim of the present work was to examine the phenolic content, antioxidant and antimicrobial effects of hydromethanolic extracts of Pinus cembra L. bark and needles. Bark extract had higher concentrations of total phenolics (299.3 vs. 78.22 mg gallic acid equivalents/g extract), flavonoids (125.3 vs. 19.84 mg catechin equivalents/g extract) and proanthocyanidins (74.3 vs. 12.7 mg cyanidin equivalents/g extract) than needle extract and was more active as a free radical scavenger, reducing agent and antimicrobial agent. The EC₅₀ values in the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and reducing power assays were 71.1, 6.3 and 26 mg/mL for bark extract and 186.1, 24 and 104 mg/mL for needle extract, respectively. In addition, needle extract showed ferrous ions chelating effects (EC₅₀ = 1,755 μg/mL). The antimicrobial effects against Staphylococcus aureus, Sarcina lutea, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans were assessed by the agar diffusion method. Both extracts (4 mg/well) were active against all the microorganisms tested; bark extract showed higher inhibition on all strains. These results indicate that Pinus cembra L. bark and needles are good sources of phytochemicals with antioxidant and antimicrobial activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 666 KiB

Open AccessArticle

Synthesis, Characterization and Fluorescent Property Evaluation of 1,3,5-Triaryl-2-pyrazolines

by Aurangzeb Hasan^1,*, Asghar Abbas² and Muhammed Nadeem Akhtar³

¹ Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur-50603, Malaysia

² Department of Chemistry, Faculty of Science, Quaid-i-Azam University, Islamabad 45320, Pakistan

³ Laboratory of Natural Products, Institute of Bioscience, University Putra Malaysia, Kuala Lumpur 43400, Malaysia

Molecules 2011, 16(9), 7789-7802; https://doi.org/10.3390/molecules16097789 - 13 Sep 2011

Cited by 59 | Viewed by 7628

Abstract

A series of 1,3,5-triaryl-2-pyrazolines was synthesized by dissolving the corresponding 4-alkoxychalcones in glacial acetic acid containing a few drops of concentrated hydrochloric acid. This step was followed by the addition of (3,4-dimethylphenyl) hydrazaine hydrochloride. Finally the target compounds were precipitated by pouring the [...] Read more.

A series of 1,3,5-triaryl-2-pyrazolines was synthesized by dissolving the corresponding 4-alkoxychalcones in glacial acetic acid containing a few drops of concentrated hydrochloric acid. This step was followed by the addition of (3,4-dimethylphenyl) hydrazaine hydrochloride. Finally the target compounds were precipitated by pouring the reaction mixture onto crushed ice. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The 1,3,5-triaryl-2-pyrazolines bearing homologous alkoxy groups were found to possess fluorescence properties in the blue region of the visible spectrum when irradiated with ultraviolet radiation. The fluorescent behavior of these compounds was studied by UV-Vis and emission spectroscopy, performed at room temperature. Full article

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12 pages, 2229 KiB

Open AccessArticle

Camptothecin-20(s)-O-[N-(3’α,12’α-dihydroxy-24’-carbonyl-5’β-cholan)]-lysine, a Novel Camptothecin Analogue, Induces Apoptosis towards Hepatocellular Carcinoma SMMC-7721 Cells

by Qingyong Li^*, Wei Qiu, Qiaochu Zhu, Yuangang Zu, Xiaoqiu Deng, Tengfei Zhao, Chunfei Jiang and Li Zhang

The Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, China

Molecules 2011, 16(9), 7803-7814; https://doi.org/10.3390/molecules16097803 - 13 Sep 2011

Cited by 13 | Viewed by 7135

Abstract

Camptothecin-20(s)-O-[N-(3’α,12’α-dihydroxy-24’-carbonyl-5’β-cholan)]-lysine (B2) is a novel camptothecin analogue. Our previous study had shown that it displayed higher cytoxicity activity towards hepatocellular carcinoma SMMC-7721 cells than camptothecin (CPT) in vitro. In this paper, the underlying mechanism of anti-proliferation of B2 [...] Read more.

Camptothecin-20(s)-O-[N-(3’α,12’α-dihydroxy-24’-carbonyl-5’β-cholan)]-lysine (B2) is a novel camptothecin analogue. Our previous study had shown that it displayed higher cytoxicity activity towards hepatocellular carcinoma SMMC-7721 cells than camptothecin (CPT) in vitro. In this paper, the underlying mechanism of anti-proliferation of B2 towards SMMC-7721 cells was further examined. Cell growth inhibition of B2 was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; morphological changes were observed under Laser Scanning Confocal Microscope (LSCM); cell cycle distribution, apoptotic population, changes in mitochondrial membrane potential, intracellular calcium concentration and reactive oxygen species (ROS) production were determined by flow cytometry (FCM). Activities of caspase-3 and caspase-9 were measured, and the expression level of Bcl-2 and Bax proteins were analyzed by Western blot. The results suggested that B2 inhibited SMMC-7721 cell growth by causing cell cycle arrest at the S and G2/M phases, and induced apoptosis involving a mitochondrial pathway. B2 appears to cause a high induction of apoptosis on SMMC-7721 cells in vitro, which suggests it might be a potential drug for cancer therapy. Full article

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29 pages, 649 KiB

Open AccessReview

Gold-Catalyzed Cyclizations of Alkynol-Based Compounds: Synthesis of Natural Products and Derivatives

by Benito Alcaide^1,*, Pedro Almendros^2,*

and José M. Alonso¹

¹ Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgánica I, Unidad Asociada al CSIC, Facultad de Química, Universidad Complutense de Madrid, 28040-Madrid, Spain

² Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006-Madrid, Spain

Molecules 2011, 16(9), 7815-7843; https://doi.org/10.3390/molecules16097815 - 13 Sep 2011

Cited by 71 | Viewed by 10862

Abstract

The last decade has witnessed dramatic growth in the number of reactions catalyzed by gold complexes because of their powerful soft Lewis acid nature. In particular, the gold-catalyzed activation of propargylic compounds has progressively emerged in recent years. Some of these gold-catalyzed reactions [...] Read more.

The last decade has witnessed dramatic growth in the number of reactions catalyzed by gold complexes because of their powerful soft Lewis acid nature. In particular, the gold-catalyzed activation of propargylic compounds has progressively emerged in recent years. Some of these gold-catalyzed reactions in alkynes have been optimized and show significant utility in organic synthesis. Thus, apart from significant methodology work, in the meantime gold-catalyzed cyclizations in alkynol derivatives have become an efficient tool in total synthesis. However, there is a lack of specific review articles covering the joined importance of both gold salts and alkynol-based compounds for the synthesis of natural products and derivatives. The aim of this Review is to survey the chemistry of alkynol derivatives under gold-catalyzed cyclization conditions and its utility in total synthesis, concentrating on the advances that have been made in the last decade, and in particular in the last quinquennium. Full article

(This article belongs to the Special Issue Gold Catalysts)

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20 pages, 1975 KiB

Open AccessReview

One Step Formation of Propene from Ethene or Ethanol through Metathesis on Nickel Ion-loaded Silica

by Masakazu Iwamoto

Chemical Resources Laboratory, Tokyo Institute of Technology, 4259-R1-5 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan

Molecules 2011, 16(9), 7844-7863; https://doi.org/10.3390/molecules16097844 - 13 Sep 2011

Cited by 58 | Viewed by 9814

Abstract

Increased propene production is presently one of the most significant objectives in petroleum chemistry. Especially the one-step conversion of ethene to propene (ETP reaction, 3C₂H₄ ® 2C₃H₆) is the most desired process. In our efforts, nickel [...] Read more.

Increased propene production is presently one of the most significant objectives in petroleum chemistry. Especially the one-step conversion of ethene to propene (ETP reaction, 3C₂H₄ ® 2C₃H₆) is the most desired process. In our efforts, nickel ion-loaded mesoporous silica could turn a new type of ETP reaction into reality. The one-step conversion of ethene was 68% and the propene selectivity was 48% in a continuous gas-flow system at 673 K and atmospheric pressure. The reactivity of lower olefins and the dependences of the ETP reaction on the contact time and the partial pressure of ethene were consistent with a reaction mechanism involving dimerization of ethene to 1-butene, isomerization of 1-butene to 2-butene, and metathesis of 2-butene and ethene to yield propene. The reaction was then expanded to an ethanol-to-propene reaction on the same catalyst, in which two possible reaction routes are suggested to form ethene from ethanol. The catalysts were characterized mainly by EXAFS and TPR techniques. The local structures of the nickel species active for the ETP reaction were very similar to that of layered nickel silicate, while those on the inert catalysts were the same as that of NiO particles. Full article

(This article belongs to the Special Issue Olefin Metathesis and Its Application)

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16 pages, 778 KiB

Open AccessArticle

Schiff Bases of Indoline-2,3-dione: Potential Novel Inhibitors of Mycobacterium Tuberculosis (Mtb) DNA Gyrase

by Tarek Aboul-Fadl^1,*, Hatem A. Abdel-Aziz¹, Mohammed K. Abdel-Hamid², Tilal Elsaman¹, Jane Thanassi³ and Michael J. Pucci³

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

² Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

³ Antimicrobial Drug Discovery, Achillion Pharmaceuticals 300 George Street New Haven, CT 06511, USA

Molecules 2011, 16(9), 7864-7879; https://doi.org/10.3390/molecules16097864 - 13 Sep 2011

Cited by 52 | Viewed by 8466

Abstract

In the present study a series of Schiff bases of indoline-2,3-dione were synthesized and investigated for their Mtb gyrase inhibitory activity. Promising inhibitory activity was demonstrated with some of these derivatives, which exhibited IC₅₀ values ranging from 50–157 mM. The orientation and [...] Read more.

In the present study a series of Schiff bases of indoline-2,3-dione were synthesized and investigated for their Mtb gyrase inhibitory activity. Promising inhibitory activity was demonstrated with some of these derivatives, which exhibited IC₅₀ values ranging from 50–157 mM. The orientation and the ligand-receptor interactions of such molecules within the Mtb DNA gyrase A subunit active site were investigated applying a multi-step docking protocol using Molecular Operating Environment (MOE) and Autodock4 docking software. The results revealed the importance of the isatin moiety and the connecting side chain for strong interactions with the enzyme active site. Among the tested compounds the terminal aromatic ring benzofuran showed the best activity. Promising new leads for developing a novel class of Mtb gyrase inhibitors were obtained from Schiff bases of indoline-2,3-dione. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 586 KiB

Open AccessArticle

Formulation and Evaluation of Celastrol-Loaded Liposomes

by Jie Song^1,†, Feng Shi^2,†, Zhenhai Zhang¹, Fenxia Zhu¹, Jing Xue¹, Xiaobin Tan¹, Luyong Zhang³ and Xiaobin Jia^1,*

¹ Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, Jiangsu, China

² Department of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

³ National Center of Drug Screening, China Pharmaceutical University, Nanjing 210038, Jiangsu, China

^† These two authors contributed equally to this work.

Molecules 2011, 16(9), 7880-7892; https://doi.org/10.3390/molecules16097880 - 13 Sep 2011

Cited by 71 | Viewed by 9215

Abstract

The main purpose of this study was to evaluate the intestinal absorption and the antineoplastic effect of the poorly water-soluble drug celastrol when liposomes were used as oral drug delivery system. Liposomes were prepared by the ethanol-injection method. An optimized liposome formulation composed [...] Read more.

The main purpose of this study was to evaluate the intestinal absorption and the antineoplastic effect of the poorly water-soluble drug celastrol when liposomes were used as oral drug delivery system. Liposomes were prepared by the ethanol-injection method. An optimized liposome formulation composed of phospholipid, cholesterol and Tween-80 resulted in favorable encapsulation efficiency at 98.06 ± 0.94%. Homogeneous and stable particle size of 89.6 ± 7.3 nm and zeta potential of −(87.7 ± 5.8) mV were determined by laser particle size analyzer. Subsequently, the four-site perfusion rat intestinal model revealed that celastrol-loaded liposomes had improved effective permeability compared to the free drug in four intestinal segments (p < 0.05). Moreover, celastrol-loaded liposomes could also inhibit the tumor growth in C57BL/6 mice. These results suggest that liposomes could be a promising perioral carrier for celastrol. Full article

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16 pages, 414 KiB

Open AccessArticle

Studies on Log P_o/w of Quinoxaline di-N-Oxides: A Comparison of RP-HPLC Experimental and Predictive Approaches

by Elsa Moreno^1,2,*, Elisabetta Gabano², Enrique Torres¹, James A. Platts³, Mauro Ravera², Ignacio Aldana¹, Antonio Monge¹ and Silvia Pérez-Silanes¹

¹ Neglected Diseases Section, Drug R&D Unit, Center for Applied Pharmacobiology Research, University of Navarra, C/ Irunlarrea s/n, 31008 Pamplona, Spain

² Dipartimento di Scienze dell’Ambiente e della Vita, Università del Piemonte Orientale “A. Avogadro”, Viale Michel 11, 15121 Alessandria, Italy

³ School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK

Molecules 2011, 16(9), 7893-7908; https://doi.org/10.3390/molecules16097893 - 13 Sep 2011

Cited by 13 | Viewed by 7859

Abstract

As reported in our previous papers, a series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and studied as anti-tuberculosis agents. Here, the capability of the shake-flask method was studied and the retention time (expressed as log K) of 20 compounds were [...] Read more.

As reported in our previous papers, a series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and studied as anti-tuberculosis agents. Here, the capability of the shake-flask method was studied and the retention time (expressed as log K) of 20 compounds were determined by RP-HPLC analysis. We found that the prediction of log P by the RP-HPLC analysis can result in a high accuracy and can replace the shake-flask method avoiding the experimental problems presented by quinoxaline di-N-oxides. The studied compounds were subjected to the ALOGPS module with the aim of comparing experimental log P_o/w values and predicted data. Moreover, a preliminary in silico screening of the QSAR relationship was made confirming the influence of reduction peak potential, lipophilicity, H-bond donor capacity and molecular dimension descriptors on anti-tuberculosis activity. Full article

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27 pages, 2960 KiB

Open AccessReview

Pyrene: A Probe to Study Protein Conformation and Conformational Changes

by Gursharan Bains¹, Arti B. Patel¹ and Vasanthy Narayanaswami^1,2,*

¹ Department of Chemistry and Biochemistry, 1250 Bellflower Boulevard, California State University Long Beach, Long Beach, CA 90840, USA

² Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA

Molecules 2011, 16(9), 7909-7935; https://doi.org/10.3390/molecules16097909 - 14 Sep 2011

Cited by 246 | Viewed by 15480

Abstract

The review focuses on the unique spectral features of pyrene that can be utilized to investigate protein structure and conformation. Pyrene is a fluorescent probe that can be attached covalently to protein side chains, such as sulfhydryl groups. The spectral features of pyrene [...] Read more.

The review focuses on the unique spectral features of pyrene that can be utilized to investigate protein structure and conformation. Pyrene is a fluorescent probe that can be attached covalently to protein side chains, such as sulfhydryl groups. The spectral features of pyrene are exquisitely sensitive to the microenvironment of the probe: it exhibits an ensemble of monomer fluorescence emission peaks that report on the polarity of the probe microenvironment, and an additional band at longer wavelengths, the appearance of which reflects the presence of another pyrene molecule in spatial proximity (~10 Å). Its high extinction coefficient allows us to study labeled proteins in solution at physiologically relevant concentrations. The environmentally- and spatially-sensitive features of pyrene allow monitoring protein conformation, conformational changes, protein folding and unfolding, protein-protein, protein-lipid and protein-membrane interactions. Full article

(This article belongs to the Special Issue Fluorophores - The Fluorescent Toolbox in Biological and Biomedical Research)

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13 pages, 577 KiB

Open AccessArticle

Chemical Profile of the Organic Residue from Ancient Amphora Found in the Adriatic Sea Determined by Direct GC and GC-MS Analysis

by Igor Jerković^1,*

, Zvonimir Marijanović², Mirko Gugić² and Marin Roje³

¹ Faculty of Chemistry and Technology, University of Split, N. Tesle 10/V, 21000 Split, Croatia

² University of Applied Sciences Marko Marulić in Knin, P. Krešimira IV 30, 22300 Knin, Croatia

³ Department of Organic Chemistry, Laboratory for Stereoselective Catalysis and Biocatalysis, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia

Molecules 2011, 16(9), 7936-7948; https://doi.org/10.3390/molecules16097936 - 14 Sep 2011

Cited by 38 | Viewed by 8061

Abstract

An ancient organic residue was collected from the bottom of a Greco-Italian amphora found in the Adriatic Sea and investigated by direct GC and GC-MS analysis. The headspace composition was determined by HS-SPME using: (1) DVB/CAR/PDMS and (2) PDMS/DVB fibres. Higher percentages of [...] Read more.

An ancient organic residue was collected from the bottom of a Greco-Italian amphora found in the Adriatic Sea and investigated by direct GC and GC-MS analysis. The headspace composition was determined by HS-SPME using: (1) DVB/CAR/PDMS and (2) PDMS/DVB fibres. Higher percentages of benzene derivatives, monoterpenes and other low-molecular aliphatic compounds were obtained by method (1) in contrast to higher percentage of naphthalene and phenanthrene derivatives found by method (2). In comparison with the composition of pine resin, it is more likely that the found low-molecular aliphatic alcohols, acids, esters and carbonyls with 2-phenylethanol were trapped and preserved within the organic residue from stored wine – the amphora’s originally content. Semi-volatile diterpenes methyl dehydroabietate (33.6%) and retene (24.1%) were dominant in the residue CH₂Cl₂ solution. Other abundant compounds were 1,4-dimethoxyphenanthrene (6.8%) as well as other naphthalene and/or phenanthrene derivatives [7-(1-methylethyl)-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydronaphthalene, 7-(1-methylethyl)-1,4a-dimethyl-2,3,4,4a,9,10-hexahydrophenanthrene, 7-(1-methylethyl)-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydro-phenanthrene, 3,6-dimethylphenanthrene and 2,3,5-trimethylphenanthrene]. Possible sources and formation pathways of the major compounds in the residue were discussed. Full article

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9 pages, 645 KiB

Open AccessArticle

Isolation and Purification of Oridonin from the Whole Plant of Isodon rubescens by High-Speed Counter-Current Chromatography

by Fa He¹, Yuhua Bai^1,*, Jing Wang¹, Jing Wei², ChunYue Yu¹, Sen Li¹, Weili Yang¹ and Chenghua Han¹

¹ College of Pharmacy, Harbin University, Daqing 163319, China

² Petrochemical Research Institute Daqing Petrochemical Research Center, Daqing 163714, China

Molecules 2011, 16(9), 7949-7957; https://doi.org/10.3390/molecules16097949 - 14 Sep 2011

Cited by 12 | Viewed by 7176

Abstract

Semi-preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of oridonin from Isodon rubescens by using a two-phase-solvent system composed of n-hexane-ethyl acetate-methanol-water (2.8:5:2.8:5, v/v/v/v). The targeted compound isolated, collected and purified by HSCCC was analyzed by high performance [...] Read more.

Semi-preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of oridonin from Isodon rubescens by using a two-phase-solvent system composed of n-hexane-ethyl acetate-methanol-water (2.8:5:2.8:5, v/v/v/v). The targeted compound isolated, collected and purified by HSCCC was analyzed by high performance liquid chromatography (HPLC). A total of 40.6 mg of oridonin with the purity of 73.5% was obtained in less than 100 min from 100 mg of crude Isodon rubescens extract. The chemical structure of the compound was identified by IR, ¹H-NMR and ¹³C-NMR. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 482 KiB

Open AccessArticle

Allicin Reduces the Production of α-Toxin by Staphylococcus aureus

by Bing-Feng Leng^1,†, Jia-Zhang Qiu^1,†, Xiao-Han Dai^1,†, Jing Dong¹, Jian-Feng Wang¹, Ming-Jing Luo¹, Hong-En Li¹, Xiao-Di Niu², Yu Zhang¹, Yong-Xing Ai^1,* and Xu-Ming Deng^1,*

¹ Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China

² College of Quartermaster Technology, Jilin University, Changchun 130062, China

^† These authors contributed equally to this work.

Molecules 2011, 16(9), 7958-7968; https://doi.org/10.3390/molecules16097958 - 15 Sep 2011

Cited by 48 | Viewed by 10295

Abstract

Staphylococcus aureus causes a broad range of life-threatening diseases in humans. The pathogenicity of this micro-organism is largely dependent upon its virulence factors. One of the most extensively studied virulence factors is the extracellular protein α-toxin. In this study, we show that allicin, [...] Read more.

Staphylococcus aureus causes a broad range of life-threatening diseases in humans. The pathogenicity of this micro-organism is largely dependent upon its virulence factors. One of the most extensively studied virulence factors is the extracellular protein α-toxin. In this study, we show that allicin, an organosulfur compound, was active against S. aureus with MICs ranged from 32 to 64 μg/mL. Haemolysis, Western blot and real-time RT-PCR assays were used to evaluate the effects of allicin on S. aureus α-toxin production and on the levels of gene expression, respectively. The results of our study indicated that sub-inhibitory concentrations of allicin decreased the production of α-toxin in both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a dose-dependent manner. Furthermore, the transcriptional levels of agr (accessory gene regulator) in S. aureus were inhibited by allicin. Therefore, allicin may be useful in the treatment of α-toxin-producing S. aureus infections. Full article

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11 pages, 377 KiB

Open AccessReview

Modulation of Animal and Human Hematopoiesis by β-Glucans: A Review

by Michal Hofer^* and Milan Pospíšil

Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Královopolská 135, CZ-61265 Brno, Czech Republic

Molecules 2011, 16(9), 7969-7979; https://doi.org/10.3390/molecules16097969 - 15 Sep 2011

Cited by 28 | Viewed by 7258

Abstract

β-Glucans are cell wall constituents of bacteria, yeast, fungi, and plants. They are not expressed in mammalian cells, but they are recognized by mammalian cells as pathogen-associated molecular patterns by pattern recognition receptors and thus act as biological response modifiers. This review summarizes [...] Read more.

β-Glucans are cell wall constituents of bacteria, yeast, fungi, and plants. They are not expressed in mammalian cells, but they are recognized by mammalian cells as pathogen-associated molecular patterns by pattern recognition receptors and thus act as biological response modifiers. This review summarizes data on the hematopoiesis-stimulating effects of β-glucans, as well as on their ability to enhance bone marrow recovery after an injury. β-Glucans have been shown to support murine hematopoiesis suppressed by ionizing radiation or cytotoxic anti-cancer therapy. They also enhance stem cell homing and engraftment. Basically, two forms of β-glucan preparations have been investigated, namely particulate and soluble ones. β-Glucans are generally well tolerated, the particulate forms showing a higher incidence of undesirable side effects. Taken together, the hematopoiesis-stimulating properties of β-glucans predetermine these biological response modifiers to ever increasing use in human medicinal practice. Full article

(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)

14 pages, 679 KiB

Open AccessReview

Thymidine Analogues for Tracking DNA Synthesis

by Brenton L. Cavanagh^1,†, Tom Walker^1,†, Anwar Norazit^1,2 and Adrian C.B. Meedeniya^1,*

¹ Health Institute and Eskitis Institute, Griffith University, Queensland 4107, Australia

² Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia

^† These authors contributed equally to the work.

Molecules 2011, 16(9), 7980-7993; https://doi.org/10.3390/molecules16097980 - 15 Sep 2011

Cited by 118 | Viewed by 14882

Abstract

Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded [...] Read more.

Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU) and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in “tagging DNA synthesis” is the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU). The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using ‘Huisgen’s reaction’ (1,3-dipolar cycloaddition or ‘click chemistry’). This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other “unnatural bases”. These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored. Full article

(This article belongs to the Special Issue Nucleoside Analogues)

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26 pages, 522 KiB

Open AccessReview

Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents

by Emmanuele Crespan, Anna Garbelli, Alessandra Amoroso and Giovanni Maga^*

DNA Enzymology & Molecular Virology, Insititute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy

Molecules 2011, 16(9), 7994-8019; https://doi.org/10.3390/molecules16097994 - 16 Sep 2011

Cited by 14 | Viewed by 9026

Abstract

The genome is constantly exposed to mutations that can originate during replication or as a result of the action of both endogenous and/or exogenous damaging agents [such as reactive oxygen species (ROS), UV light, genotoxic environmental compounds, etc.]. Cells have developed a [...] Read more.

The genome is constantly exposed to mutations that can originate during replication or as a result of the action of both endogenous and/or exogenous damaging agents [such as reactive oxygen species (ROS), UV light, genotoxic environmental compounds, etc.]. Cells have developed a set of specialized mechanisms to counteract this mutational burden. Many cancer cells have defects in one or more DNA repair pathways, hence they rely on a narrower set of specialized DNA repair mechanisms than normal cells. Inhibiting one of these pathways in the context of an already DNA repair-deficient genetic background, will be more toxic to cancer cells than to normal cells, a concept recently exploited in cancer chemotherapy by the synthetic lethality approach. Essential to all DNA repair pathways are the DNA pols. Thus, these enzymes are being regarded as attractive targets for the development of specific inhibitors of DNA repair in cancer cells. In this review we examine the current state-of-the-art in the development of nucleotide analogs as inhibitors of repair DNA polymerases. Full article

(This article belongs to the Special Issue Nucleoside Analogues)

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13 pages, 368 KiB

Open AccessReview

The Potential of Tetrandrine as a Protective Agent for Ischemic Stroke

by Yun Chen^1,2, Ya-Hui Tsai^1,2 and Sheng-Hong Tseng^3,*

¹ Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei 220, Taiwan

² Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan 320, Taiwan

³ Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan

Molecules 2011, 16(9), 8020-8032; https://doi.org/10.3390/molecules16098020 - 16 Sep 2011

Cited by 38 | Viewed by 8393

Abstract

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of [...] Read more.

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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8 pages, 419 KiB

Open AccessCommunication

Synthesis and NMR-Study of the 2,3,4,5-Tetraethylsilole Dianion [SiC₄Et₄]²⁻•2[Li]⁺

by Jang-Hwan Hong

Department of Nanopolymer Material Engineering, Pai Chai University, 155-40 Baejae-ro (Doma-Dong), Seo-Gu, Daejon 302-735, Korea

Molecules 2011, 16(9), 8033-8040; https://doi.org/10.3390/molecules16098033 - 16 Sep 2011

Cited by 13 | Viewed by 5718

Abstract

The previously unknown silole dianion [SiC₄Et₄]²⁻•2[Li]⁺ (3) was prepared by the sonication of 1,1-dichloro-2,3,4,5-tetraethyl-1-silacyclopentadiene [Cl₂SiC₄Et₄, 2] with more than four equivalent of lithium in THF. ¹H-, [...] Read more.

The previously unknown silole dianion [SiC₄Et₄]²⁻•2[Li]⁺ (3) was prepared by the sonication of 1,1-dichloro-2,3,4,5-tetraethyl-1-silacyclopentadiene [Cl₂SiC₄Et₄, 2] with more than four equivalent of lithium in THF. ¹H-, ¹³C-, and ²⁹Si-NMR data of 3 are compared with those of the reported silole dianion [SiC₄Ph₄]²⁻. Trapping of 3 with trimethylchlorosilane gave 1,1-bis(trimethylsilyl)-2,3,4,5-tetraethyl-1-silacyclopentadiene [(Me₃Si)₂SiC₄Et₄, 4] in high yield. The silole of 2 was synthesized in high yield in three steps by a modified procedure using Cp₂ZrCl₂ via Cp₂ZrC₄Et₄ and 1,4-dibromo-1,2,3,4-tetraethyl-1,3-butadiene. Full article

(This article belongs to the Special Issue Organosilicon Chemistry)

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12 pages, 562 KiB

Open AccessCommunication

Intramolecular C-H···O Hydrogen Bonding in 1,4-Dihydropyridine Derivatives

by Marina Petrova^*, Ruslan Muhamadejev, Brigita Vigante, Brigita Cekavicus, Aiva Plotniece

, Gunars Duburs and Edvards Liepinsh

Latvian Institute of Organic Synthesis Aizkraukles 21 Street, Riga LV-1006, Latvia

Molecules 2011, 16(9), 8041-8052; https://doi.org/10.3390/molecules16098041 - 19 Sep 2011

Cited by 27 | Viewed by 7664

Abstract

The diastereotopy of the methylene protons at positions 2 and 6 in 1,4-dihydropiridine derivatives with various substituents has been investigated. NMR spectroscopy and quantum chemistry calculations show that the CH···O intramolecular hydrogen bond is one of the factors amplifying the chemical shift differences [...] Read more.

The diastereotopy of the methylene protons at positions 2 and 6 in 1,4-dihydropiridine derivatives with various substituents has been investigated. NMR spectroscopy and quantum chemistry calculations show that the CH···O intramolecular hydrogen bond is one of the factors amplifying the chemical shift differences in the ¹H-NMR spectra. Full article

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9 pages, 436 KiB

Open AccessArticle

A Short Synthesis of Bisabolane Sesquiterpenes

by Zhen-Ting Du^1,2,*, Shuai Zheng¹, Gang Chen¹ and Dong Lv¹

¹ College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China

² Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Talimu University, Alaer, Xinjiang 843300, China

Molecules 2011, 16(9), 8053-8061; https://doi.org/10.3390/molecules16098053 - 19 Sep 2011

Cited by 16 | Viewed by 7858

Abstract

A facile total synthesis of three members of the bisabolane sesquiterpene family, namely (±)-curcumene, (±)-xanthorrhizol and (±)-curcuhydroquinone had been achieved in high overall yield. The synthesis used bromobenzene derivatives as starting materials. The halogen-lithium exchange followed by addition of isoprenylacetone and reduction of [...] Read more.

A facile total synthesis of three members of the bisabolane sesquiterpene family, namely (±)-curcumene, (±)-xanthorrhizol and (±)-curcuhydroquinone had been achieved in high overall yield. The synthesis used bromobenzene derivatives as starting materials. The halogen-lithium exchange followed by addition of isoprenylacetone and reduction of the obtained carbinols are the key steps of the synthetic pathway. This synthetic approach provides a new route to the bisabolane sesquiterpenes. Full article

(This article belongs to the Special Issue Terpenoids)

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14 pages, 439 KiB

Open AccessArticle

Effects of St John's Wort (Hypericum perforatum L.) Extracts on Epileptogenesis

by Vesna Ivetic^1,*, Svetlana Trivic², Marija Knezevic Pogancev¹, Mira Popovic² and Janka Zlinská³

¹ Laboratory of Neurophysiology, Department of Physiology, Medical Faculty, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia

² Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovica 3, 21000 Novi Sad, Serbia

³ University of Central Europe in Skalica, Královská 386/11, Skalica, 909 01 Trnavsky kraj, Slovakia

Molecules 2011, 16(9), 8062-8075; https://doi.org/10.3390/molecules16098062 - 19 Sep 2011

Cited by 13 | Viewed by 7512

Abstract

The purpose of this study was to investigate the effects of treatment with water, n-butanol and ether extracts of Hypercom perforatum L. on epileptogenesis in rabbits. Animals from the control group received solvent-ethanol, and the kindling model of epilepsy was used. [...] Read more.

The purpose of this study was to investigate the effects of treatment with water, n-butanol and ether extracts of Hypercom perforatum L. on epileptogenesis in rabbits. Animals from the control group received solvent-ethanol, and the kindling model of epilepsy was used. Epileptic focus was induced in Chinchilla rabbits by stimulation of the hippocampus. The following parameters were determined: the minimum current strength necessary to induce after-discharge (AD) – discharges appearing after cessation of stimulation; AD duration; the number of stimulations necessary to induce spontaneous kindling; and the latency time for the development of full kindling. The results obtained indicate that epileptogenesis is influenced by Hypericum perforatum L. extract treatment. Animals treated with an ether extract of Hypericum perforatum L. required significantly weaker minimum current strengths for the development of epileptogenic focus, and displayed longer AD times, while the number of electro-stimulations necessary for full kindling was less. In contrast, animals treated with water and n-butanol extracts required increased electro-stimulations for the development of epileptic discharge, and displayed shortened AD durations versus controls. Full article

(This article belongs to the Section Medicinal Chemistry)

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7 pages, 372 KiB

Open AccessCommunication

Two New Triterpenoids from Lysimachia heterogenea Klatt and Evaluation of Their Cytotoxicity

by Xin-An Huang¹, Xiao-Ling Shen¹, Ying-Jie Hu¹, Ya-Ming Liu², Kang-Lun Liu¹, Feng-Xue Zhang^1,* and Xin-Xin Zhou^3,*

¹ Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

² The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

³ College of Vocational and Technical Education, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

Molecules 2011, 16(9), 8076-8082; https://doi.org/10.3390/molecules16098076 - 20 Sep 2011

Cited by 11 | Viewed by 6680

Abstract

Two new 13,28-epoxy oleanane-type triterpenoids, namely heterogenoside E and F, were isolated from Lysimachia heterogenea Klatt, together with the eight known compounds: palmitic acid, β-stigmasterol, kaempferol, quercetin, hyperin, isorhamnetin, isorhamnetin-3-O-galactopyranoside and anagallisin C. Heterogenoside F possesses acetoxyl groups at the [...] Read more.

Two new 13,28-epoxy oleanane-type triterpenoids, namely heterogenoside E and F, were isolated from Lysimachia heterogenea Klatt, together with the eight known compounds: palmitic acid, β-stigmasterol, kaempferol, quercetin, hyperin, isorhamnetin, isorhamnetin-3-O-galactopyranoside and anagallisin C. Heterogenoside F possesses acetoxyl groups at the unusual C-21 and C-22 positions of its oleanane skeleton. The cytotoxic activities of anagallisin C, heterogenoside E and F were weak. Full article

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15 pages, 706 KiB

Open AccessArticle

Design and Synthesis of New N-(5-Trifluoromethyl)-1H-1,2,4-triazol-3-yl Benzenesulfonamides as Possible Antimalarial Prototypes

by Nubia Boechat^*, Luiz C.S. Pinheiro, Osvaldo A. Santos-Filho and Isabor C. Silva

Departamento de Sintese Organica, Instituto de Tecnologia em Farmacos, Fundacao Oswaldo Cruz, Manguinhos, CEP 21041-250, Rio de Janeiro, RJ, Brazil

Molecules 2011, 16(9), 8083-8097; https://doi.org/10.3390/molecules16098083 - 20 Sep 2011

Cited by 61 | Viewed by 10918

Abstract

A rational approach was used to synthesize a new set of 15 1H-1,2,4-triazol-3-yl benzenesulfonamide derivatives with the aim of developing new antimalarial lead compounds. These derivatives were prepared in yields between 50% and 62%, and their structures were elucidated using IR, [...] Read more.

A rational approach was used to synthesize a new set of 15 1H-1,2,4-triazol-3-yl benzenesulfonamide derivatives with the aim of developing new antimalarial lead compounds. These derivatives were prepared in yields between 50% and 62%, and their structures were elucidated using IR, ¹H-, ¹³C-, ¹⁹F-NMR, MS and elemental analysis. A docking study based on sulfonamides previously used against malaria identified trifluoromethyl-substituted derivatives to be the best lead compounds for new antimalarial drug development. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

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12 pages, 552 KiB

Open AccessArticle

Enzymatic Kinetic Resolution of tert-Butyl 2-(1-Hydroxyethyl)phenylcarbamate, A Key Intermediate to Chiral Organoselenanes and Organotelluranes

by Leandro Piovan, Monica D. Pasquini and Leandro H. Andrade^*

Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, SP 05508-900, São Paulo, Brazil

Molecules 2011, 16(9), 8098-8109; https://doi.org/10.3390/molecules16098098 - 20 Sep 2011

Cited by 3 | Viewed by 8195

Abstract

The enzymatic kinetic resolution of tert-butyl 2-(1-hydroxyethyl) phenylcarbamate via lipase-catalyzed transesterification reaction was studied. We investigated several reaction conditions and the carbamate was resolved by Candida antarctica lipase B (CAL-B), leading to the optically pure (R)- and (S)-enantiomers. [...] Read more.

The enzymatic kinetic resolution of tert-butyl 2-(1-hydroxyethyl) phenylcarbamate via lipase-catalyzed transesterification reaction was studied. We investigated several reaction conditions and the carbamate was resolved by Candida antarctica lipase B (CAL-B), leading to the optically pure (R)- and (S)-enantiomers. The enzymatic process showed excellent enantioselectivity (E > 200). (R)- and (S)-tert-butyl 2-(1-hydroxyethyl)phenylcarbamate were easily transformed into the corresponding (R)- and (S)-1-(2-aminophenyl)ethanols. Full article

(This article belongs to the Special Issue Enzyme-Catalyzed Reactions)

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9 pages, 444 KiB

Open AccessArticle

Solid-Phase Synthesis of a New Diphosphate 5-Aminoimidazole-4-carboxamide Riboside (AICAR) Derivative and Studies toward Cyclic AICAR Diphosphate Ribose

by Stefano D’Errico¹, Giorgia Oliviero^1,2,*

, Nicola Borbone¹, Jussara Amato¹, Vincenzo Piccialli³, Michela Varra¹, Luciano Mayol¹ and Gennaro Piccialli^1,2

¹ Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, Via D. Montesano, 49, 80131, Napoli, Italy

² Facoltà di Scienze Biotecnologiche, Università degli Studi di Napoli Federico II, Via D. Montesano, 49, 80131, Napoli, Italy

³ Dipartimento di Chimica Organica e Biochimica, Università degli Studi di Napoli Federico II, Via Cynthia, 4, 80126, Napoli, Italy

Molecules 2011, 16(9), 8110-8118; https://doi.org/10.3390/molecules16098110 - 21 Sep 2011

Cited by 23 | Viewed by 6245

Abstract

The solid-phase synthesis of the first example of a new diphosphate AICAR derivative is reported. The new substance is characterized by the presence of a 5'-phosphate group while a second phosphate moiety is installed on a 5-hydroxypentyl chain attached to the 4-N [...] Read more.

The solid-phase synthesis of the first example of a new diphosphate AICAR derivative is reported. The new substance is characterized by the presence of a 5'-phosphate group while a second phosphate moiety is installed on a 5-hydroxypentyl chain attached to the 4-N-position of AICAR. Cyclization of the diphosphate derivative by pyrophosphate bond formation allowed for the formation of a novel AICAR-based cyclic ADP-ribose (cADPR) mimic. Full article

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11 pages, 392 KiB

Open AccessArticle

Antiphytoviral Activity of Sesquiterpene-Rich Essential Oils from Four Croatian Teucrium Species

by Nada Bezić¹, Elma Vuko¹, Valerija Dunkić^1,*, Mirko Ruščić¹, Ivica Blažević² and Franko Burčul³

¹ Department of Biology, Faculty of Science, University of Split, Teslina 12, 21000 Split, Croatia

² Department of Organic Chemistry, Faculty of Chemistry and Technology, University of Split, Teslina 10, 21000 Split, Croatia

³ Department of Biochemistry, Faculty of Chemistry and Technology, University of Split, Teslina 10, 21000 Split, Croatia

Molecules 2011, 16(9), 8119-8129; https://doi.org/10.3390/molecules16098119 - 21 Sep 2011

Cited by 63 | Viewed by 8274

Abstract

The purpose of this study was to compare the essential oil profiles of four Croatian Teucrium species (Lamiaceae), as determined by GC and GC/MS, with their antiphytoviral efficiency. A phytochemical analysis showed that T. polium, T. flavum, T. montanum and T. [...] Read more.

The purpose of this study was to compare the essential oil profiles of four Croatian Teucrium species (Lamiaceae), as determined by GC and GC/MS, with their antiphytoviral efficiency. A phytochemical analysis showed that T. polium, T. flavum, T. montanum and T. chamaedrys are characterized by similar essential oil compositions. The investigated oils are characterized by a high proportion of the sesquiterpene hydrocarbons β-caryophyllene (7.1–52.0%) and germacrene D (8.7–17.0%). Other important components were β-pinene from T. montanum and α-pinene from T. flavum. The investigated essential oils were proved to reduce lesion number in the local host Chenopodium quinoa Willd. infected with Cucumber Mosaic Virus (CMV), with reductions of 41.4%, 22.9%, 44.3% and 25.7%, respectively. Full article

(This article belongs to the Special Issue Terpenoids)

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Molecules, Volume 16, Issue 9 (September 2011) – 70 articles , Pages 7183-8142

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