E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017)"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 September 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Atanas G. Atanasov

1.Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland
2. Department of Pharmacognosy, University of Vienna, Austria
Website1 | Website2 | E-Mail
Interests: molecular medicine; therapeutic targets; nutrigenomics; mechanisms of pharmacological action; cardiometabolic diseases and inflammation
Guest Editor
Prof. Dr. Josef Jampilek

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia
E-Mail
Interests: medicinal chemistry; organic synthesis; pharmaceutical analysis; drug design; structure-activity relationships; drug bioavailability; polymorphism; nanoparticles; ADME

Special Issue Information

Dear Colleagues,

The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) will be arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia. The congress will be held at the Faculty of Pharmacy in Bratislava, Slovakia on September 5–8, 2017.

The traditional symposium “Drug Synthesis and Analysis” has a long history. Over the last decade it has been transformed from a local Czech-Slovak symposium to an international conference, and now this prestigious international conference has become known as “EuroCongress on Drug Synthesis and Analysis“. These high-quality series of meetings cover all the fields of pharmaceutical sciences. The aim of ECDSA is to develop a platform for promoting cooperation between scientists sharing scientific interests in pharmaceutical/biomedical sciences from European and other countries and to support cooperation between scientists in this field. Excellent speakers from all over the world will present their results within individual sections of ECDSA-2017. For all details please see https://sites.google.com/site/cfph2017, where the full list of presenters is available, including Danica Agbaba, Marc Diederich, Norbert Haider, Yifan Han, Danijel Kikelj, Teresa Kowalska, Mark Olsen, Wei-Dong Pan, András Perczel, Robert C. Reynolds, Jerzy Silberring, Christian H. Zidorn and many others.

Participants of the conference are cordially invited to contribute original research papers or reviews to this Special Issue of Molecules.

Prof. Dr. Josef Jampilek, Ph.D.
Dr. Atanas G. Atanasov, Ph.D.
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Drug design, research and development
  • Drug formulations and drug delivery systems
  • Structure, function and interactions of proteins
  • Natural compounds
  • Structural analysis
  • Solid state analysis
  • Electrochemistry
  • Chiral compounds
  • Chemical biology
  • Biological chemistry
  • Engineered enzymes
  • Nucleic acids chemistry
  • Targeting
  • Biomaterials
  • Nanomaterials
  • Pharmacology and ADME

Published Papers (17 papers)

View options order results:
result details:
Displaying articles 1-17
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle Lipid Peroxidation Process in Meat and Meat Products: A Comparison Study of Malondialdehyde Determination between Modified 2-Thiobarbituric Acid Spectrophotometric Method and Reverse-Phase High-Performance Liquid Chromatography
Molecules 2017, 22(11), 1988; doi:10.3390/molecules22111988
Received: 28 September 2017 / Revised: 15 November 2017 / Accepted: 15 November 2017 / Published: 16 November 2017
PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this work was to compare the methods of malondialdehyde detection, as the main secondary product of the lipid peroxidation process, in meat and meat products. Malondialdehyde measurements were performed by two modified methods, the 2-thiobarbituric acid spectrophotometric method and the
[...] Read more.
The aim of this work was to compare the methods of malondialdehyde detection, as the main secondary product of the lipid peroxidation process, in meat and meat products. Malondialdehyde measurements were performed by two modified methods, the 2-thiobarbituric acid spectrophotometric method and the reverse-phase high-performance liquid chromatography in raw, mechanically-deboned chicken meat and in manufactured frankfurters. The malondialdehyde concentrations measured by the 2-thiobarbituric acid spectrophotometric method were found to be overestimated by more than 25% in raw meat and more than 27% in frankfurters in comparison to the results of reverse-phase high-performance liquid chromatography (p < 0.05). The achieved results showed that the presented modified reverse-phase high-performance liquid chromatography method was more applicable and more accurate for the quantification of malondialdehyde in samples of meat and meat products. Full article
Figures

Figure 1

Open AccessArticle Larix decidua Bark as a Source of Phytoconstituents: An LC-MS Study
Molecules 2017, 22(11), 1974; doi:10.3390/molecules22111974
Received: 6 October 2017 / Revised: 10 November 2017 / Accepted: 14 November 2017 / Published: 15 November 2017
PDF Full-text (2475 KB) | HTML Full-text | XML Full-text
Abstract
Larix decidua bark is a waste of the timber industry and is widely diffused in Northern Italy. This material can be considered a good source of antioxidants and phytoconstituents with possible use in cosmetic or nutraceutical products. In this study, simple extraction of
[...] Read more.
Larix decidua bark is a waste of the timber industry and is widely diffused in Northern Italy. This material can be considered a good source of antioxidants and phytoconstituents with possible use in cosmetic or nutraceutical products. In this study, simple extraction of larch bark was performed using mixtures of ethanol/water. Furthermore, the phytochemical composition of larch bark extract was studied using LC-MSn methods and the main constituents were identified as flavonoids, spiro-polyphenols, and procyanidins. To confirm the identification by LC-MS semi-preparative HPLC was performed in order to isolate the main constituents and verify the structures by 1H-NMR. Antioxidant properties were studied using an in vitro approach combining DPPH assay and LC-MS in order to establish different roles of the various classes of phytochemicasl of the extract. DPPH activity of some of the isolated compounds was also assessed. The overall results indicate this waste material as a good source of antioxidant compounds, mainly procyanidins, whichresulted the most active constituents in the DPPH assay. Full article
Figures

Open AccessArticle Capillary Electrophoresis Hyphenated with Mass Spectrometry for Determination of Inflammatory Bowel Disease Drugs in Clinical Urine Samples
Molecules 2017, 22(11), 1973; doi:10.3390/molecules22111973
Received: 27 October 2017 / Revised: 9 November 2017 / Accepted: 10 November 2017 / Published: 15 November 2017
PDF Full-text (522 KB) | HTML Full-text | XML Full-text
Abstract
Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a
[...] Read more.
Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a separation method based on the capillary electrophoresis (CE) hyphenated with tandem mass spectrometry (MS/MS) for the simultaneous determination of azathioprine and its selected metabolites (6-thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine) as well as other co-medicated drugs (mesalazine, prednisone, and allopurinol). The optimized CE-MS/MS conditions provided a very efficient and stable system for the separation and sensitive detection of these drugs in human urine matrices. The developed method was successfully applied for the assay of the targeted drugs and their selected metabolites in urine samples collected from patients suffering from inflammatory bowel disease (IBD) and receiving azathioprine therapy. The developed CE-MS/MS method, due to its reliability, short analysis time, production of complex clinical profiles, and favorable performance parameters, evaluated according to FDA guidelines for bioanalytical method validation, is proposed for routine clinical laboratories to optimize thiopurine therapy, estimate enzymatic activity, and control patient compliance with medication and co-medication. Full article
Figures

Figure 1

Open AccessArticle Proline-Based Carbamates as Cholinesterase Inhibitors
Molecules 2017, 22(11), 1969; doi:10.3390/molecules22111969
Received: 25 September 2017 / Revised: 28 October 2017 / Accepted: 10 November 2017 / Published: 14 November 2017
PDF Full-text (3443 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity
[...] Read more.
Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2S)-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate (IC50 = 46.35 μM) was the most potent agent. On the other hand, benzyl (2S)-2-[(4-bromophenyl)-] and benzyl (2S)-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC50 = 28.21 and 27.38 μM, respectively) comparable with that of rivastigmine. The ortho-brominated compound as well as benzyl (2S)-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure–inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA) and principal component analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3′-/4′-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE. Full article
Figures

Open AccessArticle Design, Synthesis and Anticancer Evaluation of Fangchinoline Derivatives
Molecules 2017, 22(11), 1923; doi:10.3390/molecules22111923
Received: 29 September 2017 / Revised: 1 November 2017 / Accepted: 5 November 2017 / Published: 8 November 2017
PDF Full-text (1350 KB) | HTML Full-text | XML Full-text
Abstract
Twenty fangchinoline derivatives were synthesized from the natural product fangchinoline, and their anticancer activities on human breast cancer MDA-MB-231 cell line, human prostate cancer PC3 cell line, human melanoma WM9 cell line and human leukaemia HEL and K562 cell lines were evaluated. The
[...] Read more.
Twenty fangchinoline derivatives were synthesized from the natural product fangchinoline, and their anticancer activities on human breast cancer MDA-MB-231 cell line, human prostate cancer PC3 cell line, human melanoma WM9 cell line and human leukaemia HEL and K562 cell lines were evaluated. The biological result showed that those derivatives exhibited potent activities on inhibiting cancer cell growth, and the structure-activity relationships were investigated. Among them, compound 4g, which was protected by benzoyl group in 7-phenolic position and nitrified in 14-position, showed impressive inhibition on all 5 cancer cell lines, especially WM9 cell line, with an IC50 value of 1.07 µM. Further mechanistic studies demonstrated that compound 4g may induce cancer cell death by apoptotic means. These research results suggested that compound 4g could be a lead for the further development toward an anticancer agent against human melanoma WM9 in the future. Full article
Figures

Figure 1

Open AccessArticle Natural Deep Eutectic Solvents (NADES) to Enhance Berberine Absorption: An In Vivo Pharmacokinetic Study
Molecules 2017, 22(11), 1921; doi:10.3390/molecules22111921
Received: 12 October 2017 / Revised: 3 November 2017 / Accepted: 4 November 2017 / Published: 8 November 2017
PDF Full-text (804 KB) | HTML Full-text | XML Full-text
Abstract
In the present study results related to the in vivo administration of Natural Deep Eutectic Solvents (NADES)-solubilized berberine are reported for the first time. NADES are mixtures of small natural compounds having a melting point significantly lower than that of any individual component.
[...] Read more.
In the present study results related to the in vivo administration of Natural Deep Eutectic Solvents (NADES)-solubilized berberine are reported for the first time. NADES are mixtures of small natural compounds having a melting point significantly lower than that of any individual component. Such solvents have gained much attention of the scientific community in the green chemistry area, being considered useful alternatives to common organic solvents. NADES can be used also as administration vehicles, and this can be attractive for nutraceutical products when eutectics are formed with food grade ingredients. In this work, different NADES were prepared using mainly food grade constituents and were tested as solvents for the alkaloid berberine. Three selected NADES/berberine solutions and an aqueous suspension were orally administered to mice with in dose of 50 mg/Kg. Blood levels of berberine were measured by a LC-MS/MS method. The pharmacokinetic analysis revealed a 2–20 fold increase in blood concentration of NADES/berberine with significant changes in pharmacokinetic profile. Natural Deep Eutectic Solvents may thus be considered attractive solubilizing agents and may also play a role in the increase of absorption of poorly bioavailable natural products such as berberine. Full article
Figures

Open AccessArticle Chokeberry Pomace as a Determinant of Antioxidant Parameters Assayed in Blood and Liver Tissue of Polish Merino and Wrzosówka Lambs
Molecules 2017, 22(11), 1461; doi:10.3390/molecules22111461
Received: 12 October 2017 / Revised: 30 October 2017 / Accepted: 3 November 2017 / Published: 7 November 2017
PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
Despite being a plant by-product, chokeberry pomace is believed to exert some therapeutic effects because it is one of the richest sources of highly bioavailable non-enzymatic antioxidants. The aim of this study was to determine the functionality of bioactive compounds present in the
[...] Read more.
Despite being a plant by-product, chokeberry pomace is believed to exert some therapeutic effects because it is one of the richest sources of highly bioavailable non-enzymatic antioxidants. The aim of this study was to determine the functionality of bioactive compounds present in the Aronia melanocarpa pomace (chokeberry) based on enzymatic and non-enzymatic parameters related to the active defence of liver and blood against the effects of oxidative stress. The experiment was conducted with 48 lambs of two breeds—Polish Merino and Wrzosówka. Experimental groups were administered the basic feed with the addition of 150 g or 300 g of black chokeberry pomace per each kg of the complete feed. The activities of antioxidative enzymes (superoxide dismutase, glutathione peroxidase), peptides (glutathione, glutathione disulfide), and a lipid peroxidation indicator (malondialdehyde), as well as the capacity of non-enzymatic antioxidants were investigated. The results proved a strong effect of bioactive compounds contained in the black chokeberry pomace on the estimated parameters. The inclusion of chokeberry pomace in feed mixtures brought many benefits linked with the antioxidative protection. Parameters responsible for the oxidative status were significantly modified despite the commonly-held view about a limited possibility of transferring phenolic compounds to the organs. Full article
Open AccessArticle Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis
Molecules 2017, 22(11), 1911; doi:10.3390/molecules22111911
Received: 30 September 2017 / Accepted: 3 November 2017 / Published: 6 November 2017
PDF Full-text (1110 KB) | HTML Full-text | XML Full-text
Abstract
Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA
[...] Read more.
Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA and MTX administered alone or in combination in adjuvant arthritis. The disease was induced to Lewis male rats by intradermal injection, which contains a suspension of heat-inactivated Mycobacterium butyricum in incomplete Freund’s adjuvant. The experiment of 28 days included: healthy animals, arthritic animals, arthritic animals with administration of FRA at the oral daily dose of 15 mg/kg, arthritic animals with administration of MTX at the oral dose of 0.3 mg/kg twice a week, and arthritic animals administered with FRA and MTX. FRA in monotherapy decreased significantly only the level of interleukin-1β (IL-1β) and matrix metalloproteinase-9 in plasma. Combination of FRA and low-dose MTX was more effective than MTX alone when comparing body weight, hind paw volume, arthritic score, plasmatic levels of IL-1β, activity of γ-glutamyl transferase, and relative mRNA expression of IL-1β in the spleen. Therefore, the combination treatment was the most effective. The obtained results are interesting for future possible innovative therapy of patients with RA. Full article
Figures

Figure 1

Open AccessArticle HPLC Analysis and Biochemical Characterization of LOX from Eschscholtzia californica Cham.
Molecules 2017, 22(11), 1899; doi:10.3390/molecules22111899
Received: 28 September 2017 / Revised: 31 October 2017 / Accepted: 31 October 2017 / Published: 4 November 2017
PDF Full-text (1804 KB) | HTML Full-text | XML Full-text
Abstract
Background: Plant lipoxygenases (LOXs, EC 1.13.11.12) are involved in lipid degradation, regulation of growth and development, senescence, and defence reactions. LOX represents the starting enzyme of the octadecanoid pathway. The aim of the work was to purify LOX from California poppy (Eschscholtzia
[...] Read more.
Background: Plant lipoxygenases (LOXs, EC 1.13.11.12) are involved in lipid degradation, regulation of growth and development, senescence, and defence reactions. LOX represents the starting enzyme of the octadecanoid pathway. The aim of the work was to purify LOX from California poppy (Eschscholtzia californica Cham.), to determine its biochemical properties and to identify and quantify the products of LOX reaction with unsaturated fatty acids. Methods: LOX from California poppy seedlings was purified by hydrophobic chromatography (Phenyl-Sepharose CL-4B) and by ion-exchange chromatography (Q-Sepharose). The isolated LOX was incubated with linoleic acid used as a substrate. The HPLC experiments were performed with the Agilent Technologies 1050 series HPLC system. For the preparative separation of a mixture of hydroxy fatty acids from the sample matrix, the RP-HPLC method was used (column 120-5 Nucleosil C18). Then, the NP-HPLC analysis (separation, identification, and determination) of hydroxy fatty acid isomers was carried out on a Zorbax Rx-SIL column. Results: The purified LOX indicates the presence of a nontraditional plant enzyme with dual positional specificity (a ratio of 9- and 13-hydroperoxide products 1:1), a relative molecular mass of 85 kDa, a pH optimum of 6.5, an increasing activity stimulation by CaCl2 till 2 mM, and a high substrate reactivity to linoleic acid with kinetic values of KM 2.6 mM and Vmax 3.14 μM/min/mg. Conclusions: For the first time, the LOX from California poppy seedlings was partially purified and the biochemical properties of the enzyme were analyzed. A dual positional specificity of the LOX found from California poppy seedlings is in agreement with the results obtained for LOXs isolated from other Papaveraceaes. A 1:1 ratio of 9-/13-HODE is attractive for the simultaneous investigation of both biotic stress responses (indicated by the 9-HODE marker) and the biosynthesis of jasmonic acid and jasmonates (indicated by the 13-HODE marker). Full article
Figures

Open AccessArticle A Rapid and Simple TLC-Densitometric Method for Assay of Clobetasol Propionate in Topical Solution
Molecules 2017, 22(11), 1888; doi:10.3390/molecules22111888
Received: 29 September 2017 / Revised: 31 October 2017 / Accepted: 31 October 2017 / Published: 3 November 2017
PDF Full-text (1051 KB) | HTML Full-text | XML Full-text
Abstract
A rapid, simple to use and low-cost thin-layer chromatographic procedure in normal phase system with densitometric detection at 246 nm was carefully validated according to the International Conference on Harmonisation (ICH) guidelines for assay of clobetasol propionate in topical solution containing clobetasol propionate
[...] Read more.
A rapid, simple to use and low-cost thin-layer chromatographic procedure in normal phase system with densitometric detection at 246 nm was carefully validated according to the International Conference on Harmonisation (ICH) guidelines for assay of clobetasol propionate in topical solution containing clobetasol propionate in quantity 0.50 mg/mL. The adopted thin-layer chromatographic (TLC)-densitometric procedure could effectively separate clobetasol propionate from its related compound, namely clobetasol. It is linear for clobetasol propionate in the range of 0.188 ÷ 5 µg/spot. The limit of detection (LOD) and limit of quantification (LOQ) value is 0.061 and 0.186 µg/spot, respectively. Accuracy of proposed procedure was evaluated by recovery test. The mean recovery of studied clobetasol propionate ranges from 98.7 to 101.0%. The coefficient of variation (CV, %) obtained during intra-day and inter-day studies, which was less than 2% (0.40 ÷ 1.17%), confirms the precision of described method. The assay value of clobetasol propionate is consistent with the pharmacopoeial requirements. In conclusion, it can be suitable as a simple and economic procedure for routine quality control laboratories of clobetasol propionate in topical solution. Full article
Figures

Figure 1

Open AccessArticle Ureidopyrazine Derivatives: Synthesis and Biological Evaluation as Anti-Infectives and Abiotic Elicitors
Molecules 2017, 22(10), 1797; doi:10.3390/molecules22101797
Received: 29 September 2017 / Revised: 18 October 2017 / Accepted: 20 October 2017 / Published: 23 October 2017
PDF Full-text (1658 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become a frequently deadly infection due to increasing antimicrobial resistance. This serious issue has driven efforts worldwide to discover new drugs effective against Mtb. One research area is the synthesis and evaluation
[...] Read more.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become a frequently deadly infection due to increasing antimicrobial resistance. This serious issue has driven efforts worldwide to discover new drugs effective against Mtb. One research area is the synthesis and evaluation of pyrazinamide derivatives as potential anti-TB drugs. In this paper we report the synthesis and biological evaluations of a series of ureidopyrazines. Compounds were synthesized by reacting alkyl/aryl isocyanates with aminopyrazine or with propyl 5-aminopyrazine-2-carboxylate. Reactions were performed in pressurized vials using a CEM Discover microwave reactor with a focused field. Purity and chemical structures of products were assessed, and the final compounds were tested in vitro for their antimycobacterial, antibacterial, and antifungal activities. Propyl 5-(3-phenylureido)pyrazine-2-carboxylate (compound 4, MICMtb = 1.56 μg/mL, 5.19 μM) and propyl 5-(3-(4-methoxyphenyl)ureido)pyrazine-2-carboxylate (compound 6, MICMtb = 6.25 μg/mL, 18.91 μM) had high antimycobacterial activity against Mtb H37Rv with no in vitro cytotoxicity on HepG2 cell line. Therefore 4 and 6 are suitable for further structural modifications that might improve their biological activity and physicochemical properties. Based on the structural similarity to 1-(2-chloropyridin-4-yl)-3-phenylurea, a known plant growth regulator, two selected compounds were evaluated for similar activity as abiotic elicitors. Full article
Figures

Figure 1

Open AccessArticle Silver Nanoparticles Stabilised by Cationic Gemini Surfactants with Variable Spacer Length
Molecules 2017, 22(10), 1794; doi:10.3390/molecules22101794
Received: 30 September 2017 / Revised: 18 October 2017 / Accepted: 18 October 2017 / Published: 23 October 2017
PDF Full-text (8082 KB) | HTML Full-text | XML Full-text
Abstract
The present study is focused on the synthesis and investigation of the physicochemical and biological properties of silver nanoparticles stabilized with a series of cationic gemini surfactants having a polymethylene spacer of variable length. UV-VIS spectroscopy, dynamic light scattering, scanning electron microscopy and
[...] Read more.
The present study is focused on the synthesis and investigation of the physicochemical and biological properties of silver nanoparticles stabilized with a series of cationic gemini surfactants having a polymethylene spacer of variable length. UV-VIS spectroscopy, dynamic light scattering, scanning electron microscopy and zeta potential measurements were applied to provide physicochemical characterization of the silver nanoparticles. The mean size values of the nanoparticles were found to be in the 50 to 115 nm range. From the nanoparticle size distributions and scanning electron microscopy images it results that a population of small nanoparticles with the size of several nanometers was confirmed if the nanoparticles were stabilized with gemini molecules with either a short methylene spacer (two or four −CH2− groups) or a long spacer (12 −CH2− groups). The average zeta potential value for silver nanoparticles stabilized with gemini molecules is roughly independent of gemini surfactant spacer length and is approx. +58 mV. An interaction model between silver nanoparticles and gemini molecules which reflects the gained experimental data, is suggested. Microbicidal activity determinations revealed that the silver nanoparticles stabilized with gemini surfactants are more efficient against Gram-negative bacteria and yeasts, which has a direct relation to the interaction mechanism of nanoparticles with the bacterial cell membrane and its structural composition. Full article
Figures

Open AccessArticle Caustic Ingestion in the Elderly: Influence of Age on Clinical Outcome
Molecules 2017, 22(10), 1726; doi:10.3390/molecules22101726
Received: 29 September 2017 / Revised: 10 October 2017 / Accepted: 11 October 2017 / Published: 14 October 2017
PDF Full-text (401 KB) | HTML Full-text | XML Full-text
Abstract
Caustic poisonings are still associated with many fatalities. Studies focusing on the elderly are rare. The purpose of the present study was to compare the clinical outcomes of caustic ingestion injury in elderly and non-elderly adults with regard to gender, intent of exposure,
[...] Read more.
Caustic poisonings are still associated with many fatalities. Studies focusing on the elderly are rare. The purpose of the present study was to compare the clinical outcomes of caustic ingestion injury in elderly and non-elderly adults with regard to gender, intent of exposure, substance ingested, severity of mucosal injury, complications, and mortality. Caustic substance exposures reported to the National Toxicological Information Centre in Slovakia during 1998–2015 were reviewed retrospectively. The patients were divided into two groups: the non-elderly (<60 years) and elderly adults (≥60 years). The mortality rate in the elderly was significantly higher (elderly 23.0% vs. non-elderly 11.3%; p = 0.041). The risk of fatal outcome in the elderly was increased by acid ingestion (OR = 7.822; p = 0.002), particularly hydrochloric acid (OR = 5.714, p = 0.006). The incidence of respiratory complications was almost two times higher in the elderly was 31.1% vs. 17.4% for the non-elderly (p = 0.037). Respiratory complications significantly correlated with an increased mortality rate (p = 0.001) in the elderly whereas there was no association between GI complications and mortality in the elderly (p = 0.480). Elderly patients with respiratory complications had the poorest clinical outcomes. The highest risk of complications and fatalities was observed in patients after hydrochloric acid ingestion. Full article
Figures

Figure 1

Open AccessArticle Halogenated 1-Hydroxynaphthalene-2-Carboxanilides Affecting Photosynthetic Electron Transport in Photosystem II
Molecules 2017, 22(10), 1709; doi:10.3390/molecules22101709
Received: 21 September 2017 / Accepted: 9 October 2017 / Published: 12 October 2017
PDF Full-text (977 KB) | HTML Full-text | XML Full-text
Abstract
Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides substituted in the anilide part by
[...] Read more.
Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides substituted in the anilide part by 3,5-dichloro-, 4-bromo-3-chloro-, 2,5-dibromo- and 3,4,5-trichloro atoms were the most potent PET inhibitors (IC50 = 5.2, 6.7, 7.6 and 8.0 µM, respectively). The inhibitory activity of these compounds depends on the position and the type of halogen substituents, i.e., on lipophilicity and electronic properties of individual substituents of the anilide part of the molecule. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB in the PET chain occurring on the acceptor side of PS II can be suggested as the site of action of the compounds. The structure-activity relationships are discussed. Full article
Figures

Open AccessArticle Two-Dimensional Capillary Electrophoresis with On-Line Sample Preparation and Cyclodextrin Separation Environment for Direct Determination of Serotonin in Human Urine
Molecules 2017, 22(10), 1668; doi:10.3390/molecules22101668
Received: 26 September 2017 / Revised: 3 October 2017 / Accepted: 4 October 2017 / Published: 7 October 2017
PDF Full-text (1407 KB) | HTML Full-text | XML Full-text
Abstract
An advanced two-dimensional capillary electrophoresis method, based on on-line combination of capillary isotachophoresis and capillary zone electrophoresis with cyclodextrin additive in background electrolyte, was developed for effective determination of serotonin in human urine. Hydrodynamically closed separation system and large bore capillaries (300–800 µm)
[...] Read more.
An advanced two-dimensional capillary electrophoresis method, based on on-line combination of capillary isotachophoresis and capillary zone electrophoresis with cyclodextrin additive in background electrolyte, was developed for effective determination of serotonin in human urine. Hydrodynamically closed separation system and large bore capillaries (300–800 µm) were chosen for the possibility to enhance the sample load capacity, and, by that, to decrease limit of detection. Isotachophoresis served for the sample preseparation, defined elimination of sample matrix constituents (sample clean up), and preconcentration of the analyte. Cyclodextrin separation environment enhanced separation selectivity of capillary zone electrophoresis. In this way, serotonin could be successfully separated from the rest of the sample matrix constituents migrating in capillary zone electrophoresis step so that human urine could be directly (i.e., without any external sample preparation) injected into the analyzer. The proposed method was successfully validated, showing favorable parameters of sensitivity (limit of detection for serotonin was 2.32 ng·mL−1), linearity (regression coefficient higher than 0.99), precision (repeatability of the migration time and peak area were in the range of 0.02–1.17% and 5.25–7.88%, respectively), and recovery (ranging in the interval of 90.0–93.6%). The developed method was applied for the assay of the human urine samples obtained from healthy volunteers. The determined concentrations of serotonin in such samples were in the range of 12.4–491.2 ng·mL−1 that was in good agreement with literature data. This advanced method represents a highly effective, reliable, and low-cost alternative for the routine determination of serotonin as a biomarker in human urine. Full article
Figures

Figure 1

Review

Jump to: Research, Other

Open AccessReview How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair
Molecules 2017, 22(11), 1818; doi:10.3390/molecules22111818
Received: 21 September 2017 / Accepted: 20 October 2017 / Published: 26 October 2017
PDF Full-text (1771 KB) | HTML Full-text | XML Full-text
Abstract
It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive
[...] Read more.
It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids. Full article
Figures

Figure 1

Other

Jump to: Research, Review

Open AccessConference Report The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot
Molecules 2017, 22(11), 1848; doi:10.3390/molecules22111848
Received: 29 September 2017 / Revised: 26 October 2017 / Accepted: 26 October 2017 / Published: 28 October 2017
PDF Full-text (5477 KB) | HTML Full-text | XML Full-text
Abstract
The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5–8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical
[...] Read more.
The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5–8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, “Drug Synthesis and Analysis,” meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting. Full article
Figures

Figure 1

Back to Top