Proceedings of 4th International Electronic Conference on Medicinal Chemistry最新文献

{"title":"In vitro antidiabetic evaluation guided by GC-MS analysis of ethyl acetate leaves extract of Acacia auriculiformis Benth.","authors":"N. Rangra, S. Samanta, K. Pradhan","doi":"10.3390/ecmc-4-05603","DOIUrl":"https://doi.org/10.3390/ecmc-4-05603","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73451041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro drug-drug interaction studies of Gliclazide with Levofloxacin by using HPLC: guidelines for co-prescription drugs","authors":"S. Chhajed, H. Chaudhari, Yatish R. Rajderkar, Akshada Pingle, S. Sonawane, S. Kshirsagar","doi":"10.3390/ecmc-4-05586","DOIUrl":"https://doi.org/10.3390/ecmc-4-05586","url":null,"abstract":"A simple, accurate reversed-phase high-performance liquid chromatography method was developed and validated for simultaneous determination of gliclazide (GLZ) and fluoroquinolone antibacterial levofloxacin (LVO). The method was developed by using a stainless steel analytical column , C18 (250,4.6 mm,5µm). The system was operated using a mobile phase consisting of methanol and phosphate buffer (pH 3.0) at a flow rate of 0.8mL minˉ1 with ultraviolet detection monitored at wavelength 228 nm. The above method was validated using ICH analytical method validation guidelines. Utilizing HPLC techniques, an assay was intended to determine in vitro effects of levofloxacin on sulphonyl urea an anti-diabetic gliclazide. Obtained results were further verified with UV spectrophotometric method. Availability of gliclazide was reduced in the presence of levofloxacin. This in vitro analyses confirms the co-administration of gliclazide and levofloxacin and may serve for designing further in vivo studies.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82181487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking analyses of thiazolidine-2,4-dione analogues for PPAR-gamma agonism in the search of antidiabetic agents","authors":"S. Chhajed, Vandana Jadhav, H. Mahajan, S. Kshirsagar","doi":"10.3390/ecmc-4-05596","DOIUrl":"https://doi.org/10.3390/ecmc-4-05596","url":null,"abstract":"In the present work, molecular docking analyses of few thiazolidinediones into the catalytic domain of protein PPAR-gamma is reported for the discovery of antidiabetic agents. Protein PPARgamma is involved in carbohydrate and fat metabolism hence it will be a useful target for treating type-2 diabetes. With this view, mapping of ligand binding domain of protein PPAR-gamma was carried out using online server such as uniport; pharmacophoric points using co-crystal rosiglitazone were studied. Molecular docking of thiazolidine-2,4-diones was carried out using Vlife MDS suite. Binding energy and interactions such as hydrogen bond, Vander Wall pi stacking and hydrophobic interactions, which happened between ligands and the protein, have been studied. Compounds exhibiting strong affinity and interactions in the pocket where rosiglitazone binds will be taken for wet laboratory synthesis.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91162235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial activity of cyclam derivatives","authors":"Luis G. Alves, J. Portel, S. A. Sousa, J. Leitão, Ana M. Martins","doi":"10.3390/ecmc-4-05595","DOIUrl":"https://doi.org/10.3390/ecmc-4-05595","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81015987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologically-active sulfated steroids: synthesis and state-of-art","authors":"Francisca Carvalhal, A. Neves, Amadeu Câmara, E. Sousa, M. Pinto, M. Correia-da-Silva","doi":"10.3390/ecmc-4-05574","DOIUrl":"https://doi.org/10.3390/ecmc-4-05574","url":null,"abstract":"Several biological activities from nearly 150 marine-derived sulfated steroids have been reported with both pharmacological (antimicrobial, antitumor, cardiovascular and/ or anti-inflammatory activities) and environmental (antifouling activity) applications [1]. Sulfation is used in Nature to avoid toxicity and therefore marine-inspired sulfated steroids could be an interesting strategy for drug discovery. The sulfated aminosterol squalamine, isolated from the internal organs of the dogfish shark, is in phase III of clinical trials as anti-angiogenic drug [2], which evidences the potential of sulfated steroids. \u0000Sulfation of small molecules using sulfur trioxide-amine complexes entails several advantages, such as persulfation, low degradation, and feasibility in the work-up [3]. Moreover, these complexes appear to be suitable for sulfation of alcohol groups present in steroids [4]. In this direction, sulfation of four sterols was achieved using triethylamine-sulfur trioxide adduct in dimethylacetamide under heating, with yields ranging from 3% to 93%. Purification involved insolubilization with diethyl ether followed by several methods to obtain the sulfated derivatives free of inorganic impurities, including dialysis and/ or chromatographic processes. Structure elucidation of these new compounds was established by infrared (IR), nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS). Biological activities will be further studied. \u0000 \u0000 \u0000Acknowledgements: \u0000This work was supported through national funds provided by FCT/MCTES - Foundation for Science and Technology from the Ministry of Science, Technology and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) through the COMPETE Programa Operacional Factores de Competitividade (POFC) programme, under the projects PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599–PPCDT), PTDC/AAGTEC/0739/2014 (reference POCI-01-0145-FEDER-016793; Project 9471-RIDTI) and POCI-01-0145-FEDER-028736 in the framework of the programme PT2020. Carvalhal F also acknowledges FCT for the grant PTDC/AAG- TEC/0739/2014-018. \u0000 \u0000References: \u0000[1] Carvalhal, F., M. Correia-da-Silva, M.E. Sousa, M. Pinto, and A. Kijjoa, Journal of Molecular Endocrinology, 2018, 61(2) 211-231. \u0000[2] NCT02727881 (https://clinicaltrials.gov/ct2/show/NCT02727881, October 15, 2018) \u0000[3] Correia-da-Silva, M., E. Sousa, and M.M. Pinto, Medicinal Research Reviews, 2014, 34(2) 223-79. \u0000[4] Al-Horani, R.A., and U.R. Desai, Chemical Sulfation of Small Molecules - Advances and Challenges.Tetrahedron, 2010, 66(16), 2907-2918","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77708805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New 2-alkylthio-4-chlorobenzenesulfonamide derivatives bearing heterocyclic moieties – synthesis, structure and anticancer activity studies","authors":"B. Żołnowska, J. Sławiński, Aneta Pogorzelska, Krzysztof Szafrański, A. Kawiak, Mariusz Belka, T. Bączek, J. Chojnacki","doi":"10.3390/ECMC-4-05587","DOIUrl":"https://doi.org/10.3390/ECMC-4-05587","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83250849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking analysis of S-alkyl derivatives of thiosalicylic acid as cyclooxygenase inhibitor agents","authors":"M. Mijajlovic, M. Nikolic, V. Dobričić, Z. Vujić, A. Bukonjic, D. Tomović, Aleksandar Kočović, V. Jevtić, Z. Ratković, S. Trifunović, G. Radić","doi":"10.3390/ECMC-4-05609","DOIUrl":"https://doi.org/10.3390/ECMC-4-05609","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79568154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative activity of steroidal oxime and its O-alkylated derivatives","authors":"Jovana J. Ajduković, M. Filipovic, M. Perkovic, Elizabeta Stanić, D. Jakimov","doi":"10.3390/ECMC-4-05569","DOIUrl":"https://doi.org/10.3390/ECMC-4-05569","url":null,"abstract":"Oxime ethers have attracted much interest as important precursors and intermediates for the preparation of a wide variety of drugs and natural products. They can be easily converted into important functional groups such as amino alcohols and hydroxy ketones. Therefore, the development of methodologies for the preparation of oxime ethers is of considerable interest. Various researchers have studied the interesting biological properties of oxime ether derivatives such as anticonvulsant, anti-inflammatory, antineoplastic, anti-enteroviral, antimicrobial, antitumor, and anti-Helicobacter pylori activities [1].\u0000Since clinical use of almost all anticancer drugs has been limited by the toxicity to normal tissues, important goal of cancer chemotherapy is to amplify the selective inhibition of tumor cells while decreasing toxicity to normal tissues.\u0000In order to develop more efficient and selective antitumor agents, here we report the efficient synthesis of 17-substituted O-alkylated androstane derivatives, and investigate their antiproliferative activity (IC50 after 72 h, MTT test) against three tumor cell lines (MDA-MB-231, HeLa and HT-29) and one healthy cell line (MRC-5).\u0000In continuation of our work on nitrogen containing androstane derivatives [2-4], synthesis of respective novel compounds and their evaluation in a human carcinoma cell lines will be presented and discussed.\u0000\u0000Acknowledgements:\u0000This work was financialy supported by Ministry of Education, Science and Technological development of the Republic of Serbia (Project No. 172021).\u0000\u0000[1] K. Sharma, S. B. Mishra, A. K. Mishra, Helv. Chim. Acta 94 (2011), 2256.\u0000[2] J. Ajdukovic, E. Djurendic, E. Petri, O. Klisuric, A. Celic, M. Sakac, D. Jakimov, K. Penov Gasi, Bioorg. Med. Chem. 21 (2013), 7257.\u0000[3] E. Djurendic, J. Ajdukovic, M. Sakac, J. Csanadi, V. Kojic, G. Bogdanovic, K. Penov Gasi, Eur. J. Med. Chem. 54 (2012), 784.\u0000[4] J. J. Ajdukovic, K. M. Penov Gasi, D. S. Jakimov, O. R. Klisuric, S. S. Jovanovic-Santa, M. N. Sakac, L. D. Aleksic, E. A. Djurendic, Bioorg. Med. Chem. 23 (2015), 1557.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73728473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trojan horse strategy: synthesis of piperazine-based siderophores","authors":"P. Loupias, A. Dassonville-Klimpt, Elodie Lohou, N. Taudon, P. Sonnet","doi":"10.3390/ecmc-4-05579","DOIUrl":"https://doi.org/10.3390/ecmc-4-05579","url":null,"abstract":"Resistance to antibiotics is an emerging phenomenon and a major medical problem. The resistance of Gram-negative bacteria such as Pseudomonas aeruginosa and the Burkholderia group to conventional antibiotics leads to therapeutic failure and requires new antibiotic therapies. The use of iron transport systems is a promising strategy to overcome this phenomenon. These TonB-dependent receptors, essential for the survival of microorganisms, allow specific recognition of ferric siderophore complexes in order to transport iron within bacteria1. Bacteria, according to their kind, express different types of receptors that allow them to recognize their endogenous siderophores but also xenosiderophores. Pseudomonas aeruginosa and Burkholderia pseudomallei in particular possess FptA receptors allowing the recognition of pyochelin.2 These specific systems may allow the introduction of antibacterial agents by forming antibiotic-siderophore conjugates or toxic complexes such as gallium complexes, in the bacteria to kill it. Siderophores have three types of chelating function: catechols, hydroxamates and hydroxy-carboxylates. Previous work in the laboratory has shown that piperazine 1,4-dicatechol structures (MPPS0225) could be recognized by Pseudomonas aeruginosa strains. In order to further investigate this piperazine platform, we have synthesized iron chelators bearing 3-hydroxypyridin-4-ones and 1,3-dihydroxypyridin-4-one ligands. At the same time, we were interested in the synthesis of a more complex 2,5-dioxopiperazine platform, part of the rhodotorulic acid (RA), a natural siderophore produced by Rhodotorula pilimanae showing an interesting iron affinity (pFe = 21,8). Two RA synthesis strategies will be developed as well as the corresponding 3,6-disubstituted analogs. Through the synthesis of these chelators, we would like to study the influence, on the iron complexation, of: i) the nitrogen platform (piperazine or dioxopiperazine), ii) the presence of stereogenic centers (3,6-disubstituted dioxopiperazine vs 1,4 -disubstituted piperazines) and iii) the nature of the iron ligands (hydroxypyridinone vs catechol). An evaluation of the siderophore-like potential and a measurement of the complexing force will be carried out. \u0000We would like to thank the DGA and the Haut de France region for their financial support.\u0000References\u0000\u0000Miethke M.; Marahiel MA. Microbiology and Molecular Biology Reviews. 2007, 71, 413-451.\u0000 Butt AT.; Thomas MS. Frontiers in Cellular and Infection Microbiology. 2017, 7.","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74730612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the metabolomic signature of diabetes and the oral glucose tolerance test","authors":"Álvaro González-Domínguez, A. Lechuga-Sancho, R. González-Domínguez","doi":"10.3390/ecmc-4-05571","DOIUrl":"https://doi.org/10.3390/ecmc-4-05571","url":null,"abstract":"Intervention trials attempt to clarify the possible effects of certain challenge tests on study subjects (e.g. drugs effectiveness, environmental exposure experiments), while observational studies employ free-living populations to analyze the relationship between a particular effect and possible triggering factors. Based on the hypothesis under investigation, the researcher will choose the appropriate study design. Nevertheless, here we report the utility of combining observational and interventional studies to discover confident biomarkers in the clinical field (1). We contrasted metabolomic profiles related with diabetes and the oral glucose tolerance test (OGTT), a clinical test used to simulate the hyperinsulinemia observed in diabetes. We found that the main metabolic changes occur in the same metabolite classes, including energy-related metabolites, amino acids (especially brain chain amino acids, BCAA) and multiple lipids, such as free fatty acids, acyl-carnitines, triglycerides and phospholipids, among them. Hence, challenge tests such as the OGTT guarantee to be a great strategy to investigate pathological signatures associated with the development of diseases as a previous step before performing validation works in observational studies. \u0000 (1) A. Gonzalez-Dominguez, A.M. Lechuga-Sancho, R. Gonzalez-Dominguez. Intervention and Observational Trials are Complementary in Metabolomics: Diabetes and the Oral Glucose Tolerance Test. Curr. Top. Med. Chem. 18 (2018) 896-900","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78875898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}