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

N-Acylhydrazone derivatives as potent histone deacetylase 6 inhibitors n -酰基腙衍生物作为有效的组蛋白去乙酰化酶6抑制剂

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ecmc-4-05584

C. Fraga, Daniel C. Rodrigues, P. S. M. Pinheiro, M. A. Alves, R. Gomes, L. Chaves, Guilherme A. Ferreira-Silva, Ana C. S. Ferreira, R. A. Fernandes, J. Kwee, C. M. R. Sant’Anna, M. Ionta

引用次数: 0

In silico study of the polymyxin resistance in the genomes of Pseudomonas aeruginosa 铜绿假单胞菌基因组中多粘菌素耐药性的计算机研究

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ecmc-4-05583

J. G. Carneiro, Cindy Magda Araújo dos Santos Freire, Marcelo Lopes Moreira, Manuela Araújo Carneiro, José Edvar Monteiro Júnior, José E. C. Freire

引用次数: 0

Anticancer and antimicrobial activity of new C-28 guanidine-functionalized triterpenoic acid derivatives. 新的C-28胍功能化三萜酸衍生物的抗癌和抗菌活性。

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ecmc-4-05573

A. Spivak, R. Khalitova, D. Nedopekina, L. Dzhemileva, M. Yunusbaeva, V. Odinokov, V. D’yakonov, U. Dzhemilev

{"title":"Anticancer and antimicrobial activity of new C-28 guanidine-functionalized triterpenoic acid derivatives.","authors":"A. Spivak, R. Khalitova, D. Nedopekina, L. Dzhemileva, M. Yunusbaeva, V. Odinokov, V. D’yakonov, U. Dzhemilev","doi":"10.3390/ecmc-4-05573","DOIUrl":"https://doi.org/10.3390/ecmc-4-05573","url":null,"abstract":"Novel betulinic, ursolic, and oleanolic acid derivatives, containing a guanidine moiety have been designed and synthesized in an attempt to develop potent antitumor, antibacterial and antifungal agents. Triterpenoic acids were converted into C-28-aminotriterpenoids in which polyamine moieties were bound with C-28 carboxylic group through an amide or ester bonds. These compounds served as precursors for the synthesis of novel guanidine-functionalized triterpenoic acids derivatives. The cytotoxicity was tested on five human tumor cell lines (Jurkat, K562, U937, HEK, and Hela) and compared with the tests on normal human fibroblasts. The antitumor activities of the most tested guanidine derivatives was lower than that of corresponding amines, but triterpenoids with the guanidine group were less toxic to human fibroblasts. The identified lead molecules with the highest antitumor characteristics were selected for extensive biological testing according to flow cytometry data, which showed that the antitumor activity of these compounds is caused by apoptotic processes and induction of cell cycle arrest in the S-phase. Most of the tested guanidine derivatives showed a good antibacterial effect against Gram-positive bacteria Staphylococcus aureus (MICs values 0.5-4.0 mg/mL) and expressed significant antifungal activity against Candida albicans (4.0 mg/mL) and Cryptococcus neoformans (0.25-4.0 mg/mL), higher than the standard fluconazole (8.0 mg/mL).","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":"78230505","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}

引用次数: 0

Optimization of phenolic compounds extraction conditions from lady's bedstraw (Galium verum L.) using historical data design 采用历史数据设计法优化妇草中酚类化合物的提取工艺

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ECMC-4-05600

Aleksandar Kočović, Miroslav Sovrlić, M. Tomovic, Jovana V Bradic, A. Petkovic

{"title":"Optimization of phenolic compounds extraction conditions from lady's bedstraw (Galium verum L.) using historical data design","authors":"Aleksandar Kočović, Miroslav Sovrlić, M. Tomovic, Jovana V Bradic, A. Petkovic","doi":"10.3390/ECMC-4-05600","DOIUrl":"https://doi.org/10.3390/ECMC-4-05600","url":null,"abstract":"Lady's bedstraw (Galium verum L.) are often used in the traditional medicine of the Balkan countries. In previous studies it has been shown that the main components of G. verum extracts, phenols and flavonoids are in the form of heterosides with different saccharides. Also, different types of terpenes, which are the main components of essential oil, are present. In this study, we wanted to identify the optimal conditions for the extraction of phenolic compounds from G. verum. For extraction we used methanol, 96% ethanol and 70% ethanol at five time intervals (15, 30, 60, 90 and 120 minutes). Extraction was carried out in conical flasks, on a shaker, at room temperature (25°C). The total phenolic content in the extracts was determined spectrophotometrically, using the standard method with the Folin–Ciocalteu reagent, and the results were expressed as gallic acid equivalents (GAE – mg of gallic acid/g of crude extract). The total phenolic content when 70% ethanol was used were 33.36±1.94, 64.06±1.51, 112.36±3.23, 141.40±3.06 and 142.77±3.28 GAE in 15, 30, 60, 90 and 120 minute respectively. We used historical data design (HDD) in Design Expert 7.0 software to identify optimal extraction conditions. ANOVA analysis showed that there is a statistically significant difference in the amount of extracted phenols in between all time intervals except between 90 and 120 minutes. The results of the optimization analysis showed that the highest yield of total phenols (145.78 GAE) was obtained using 70% ethanol as a solvent in a time of 107.03 minutes (desirability level = 0.996), while the lowest yield was obtained using methanol as a solvent. Equation of model when 70% ethanol is used as a solvent is: Total phenols = 0.26 + 2.30 ∗time + 4.74^−3 ∗ time^2 − 3.70^−5 ∗ time^3. The experimental values agreed with those predicted, thus indicating suitability of the model employed and the success of HDD in optimizing the extraction conditions.","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":"78960725","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}

引用次数: 0

Dual application of chiral derivatives of xanthones in medicinal chemistry and liquid chromatography 山酮类手性衍生物在药物化学和液相色谱中的双重应用

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ecmc-4-05604

C. Fernandes, Ye' Zaw Phyo, João Ribeiro, S. Cravo, M. Tiritan, Artur M. S. Silva, A. Kijjoa, M. Pinto

{"title":"Dual application of chiral derivatives of xanthones in medicinal chemistry and liquid chromatography","authors":"C. Fernandes, Ye' Zaw Phyo, João Ribeiro, S. Cravo, M. Tiritan, Artur M. S. Silva, A. Kijjoa, M. Pinto","doi":"10.3390/ecmc-4-05604","DOIUrl":"https://doi.org/10.3390/ecmc-4-05604","url":null,"abstract":"Over several years, xanthone derivatives have been the core of several studies, essentially due their wide range of biological and pharmacological activities [1]. Recently, chiral derivatives of xanthones (CDXs) have come to arouse great interest considering enantioselectivity studies associated with biological activities [2,3] as well as selectors for chiral stationary phases (CSPs) in liquid chromatography (LC) [4,5]. \u0000From the perspective of Medicinal Chemistry, some CDXs synthetized by our group revealed interesting biological activities [2,3]. Besides the potential as new drugs, CDXs afford promising LC enantioresolution results [6]. \u0000In a continuation of our study, new enantiomerically pure CDXs were synthetized for biological activity evaluation as well as selectors for new CSPs, confirming that CDXs have important applications not only in the field of Medicinal Chemistry but also for analytical applications. \u0000Acknowledgements: \u0000This research was partially supported by the Strategic Funding UID/Multi/04423/2013 and UID/QUI/00062/2013 through national funds provided by FCT and ERDF, in the framework of PT2020, by projects PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599-PPCDT), and project No. POCI-01-0145-FEDER-028736, co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by FCT through national funds, as well as by the Portuguese NMR Network, and CHIRALXANT-CESPU-2018. \u0000 \u0000[1] Shagufta, A.I. Eur. J. Med. Chem., 2016, 116, 267-280. \u0000[2] Fernandes, C. et al. Bioorg. Med. Chem. 2014, 22, 1049-1062. \u0000[3] Fernandes, C. et al. Pharmaceuticals, 2017, 10, 50, doi:10.3390/ph10020050. \u0000[4] Phyo, Y.Z. et al. Molecules, 2018, 23, 142, doi:10.3390/molecules23010142. \u0000[5] Carraro, M.L. et al. Chirality, 2017, 1–10 \u0000[6] Fernandes, C. et al. Chirality, 2017, 29(8),430-442.","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":"87569424","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}

引用次数: 0

Synthesis and study of new antitubercular compounds 新型抗结核化合物的合成与研究

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ecmc-4-05578

P. Laumaillé, A. Dassonville-Klimpt, P. Sonnet

{"title":"Synthesis and study of new antitubercular compounds","authors":"P. Laumaillé, A. Dassonville-Klimpt, P. Sonnet","doi":"10.3390/ecmc-4-05578","DOIUrl":"https://doi.org/10.3390/ecmc-4-05578","url":null,"abstract":"Tuberculosis is regarded as one of the deadliest diseases in the world. It is a bacterial infection caused by some bacteria from the genus Mycobacterium, such as Mycobacterium tuberculosis. Some bacterial strains are multi-resistant or extensively-resistant against classical antibiotics. Consequently, there is a necessity to set up new strategies to prevent the spread of antibiotic resistant mycobacteria. Quinoline core is present in some antitubercular compounds. Indeed, bedaquiline (one of the last commercialized antitubercular compounds) is a diarylquinoline, which acts by inhibiting selectively the mycobacterial ATP synthase. This enzyme is required for the energetic metabolism of the cell and is a critical target to kill dormant strains. Mefloquine is a quinoline used as antimalarial compound but this molecule shows also antimycobacterial properties. Mefloquine can inhibit ATP synthase of Streptococcus pneumoniae, this inhibition may explain it antimycobacterial activity. The objectives of this work are designing, synthesizing, and evaluating new antitubercular compounds as quinoline derivatives (AQM). These molecules are expected to inhibit mycobacterial ATP synthase in order to fight latent forms of mycobacteria. The previous works of the research team have allowed to identify a lead compound which shows an MIC of 1 μM against M. tuberculosis MtbH37Rv strain. A pharmacomodulation of this lead compound will be shown here.","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":"87484842","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}

引用次数: 0

Z-Stereoselective catalytic synthesis of natural acids, lembehynes, and acetogenins - Modern preparations for medicine z -立体选择性催化合成天然酸、lembehynes和醋酸原。现代药物制剂

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ECMC-4-05613

V. D’yakonov, L. Dzhemileva, R. A. Tuktarova, A. A. Makarov, Svetlana R. Ishmukhametova, E. Andreev, U. Dzhemilev

引用次数: 0

Effect of Senecio serratuloides and its bioactive compound on hypertension 蛇耳草及其活性化合物对高血压的影响

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ecmc-4-05602

C. Sewani-rusike, C. Tata, D. Ndinteh, B. Nkeh-Chungag, O. O. Oyedeji

引用次数: 0

A stability indicating RP-HPLC method development and validation for the estimation of combined tablet formulation of Amlodipine & Candesartan 氨氯地平坎地沙坦联合片剂处方稳定性指示反相高效液相色谱法的建立与验证

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ECMC-4-05585

S. D. Patil, Sunil V. Amurutkar, C. Upasani

{"title":"A stability indicating RP-HPLC method development and validation for the estimation of combined tablet formulation of Amlodipine & Candesartan","authors":"S. D. Patil, Sunil V. Amurutkar, C. Upasani","doi":"10.3390/ECMC-4-05585","DOIUrl":"https://doi.org/10.3390/ECMC-4-05585","url":null,"abstract":"A stability indicating High Performance Liquid Chromatographic (HPLC) method was developed and validated for the estimation of combined tablet formulation of Amlodipine & Candesartan. Chromatographic separation was optimized by Binary Gradient System HPLC on a Grace C18 (250mm x 4.6ID, Particle size: 5 micron) utilizing a mobile phase consisting a methanol: phosphate buffer (pH-3, adjusted with 0.1% OPA) 80:20 % v/v at a flow rate of 0.8ml/min with UV-3000-M at 244nm. The retention time of Amlodipine & Candesartan was 4.2min and 6.3 min respectively.\u0000Good linearity was obtained over the range of 5 μg/ml to 25 μg/ml & 8 μg/ml to 40 μg/ml for Amlodipine & Candesartan. Correlation coefficient was found to be 0.999 for both derivatives. The % RSD of precision Amlodipine & Candesartan was found to be 0.54 and 0.60 respectively. The % mean recovery was found to 98.93-99.00 % for Amlodipine and 99.75-99.87 %for Candesartan. The results obtained for accuracy, precision, LOD, LOQ and Ruggedness were within the limits. Thus the validated economical method was applied for forced degradation study of Amlodipine & Candesartan tablets.","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":"74078090","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}

引用次数: 1

Conception of DYRK1A kinase inhibitors via metal-catalyzed C–H arylation, inspired by fragment-growing studies 受片段生长研究启发，通过金属催化的C-H芳基化构建DYRK1A激酶抑制剂

Proceedings of 4th International Electronic Conference on Medicinal Chemistry Pub Date : 2018-10-31 DOI: 10.3390/ecmc-4-05580

Florence Couly, J. Diharce, P. Bonnet, M. Laurent, Corinne Fruit, T. Besson

{"title":"Conception of DYRK1A kinase inhibitors via metal-catalyzed C–H arylation, inspired by fragment-growing studies","authors":"Florence Couly, J. Diharce, P. Bonnet, M. Laurent, Corinne Fruit, T. Besson","doi":"10.3390/ecmc-4-05580","DOIUrl":"https://doi.org/10.3390/ecmc-4-05580","url":null,"abstract":"The search for therapeutic inhibitors of specific kinases has been developed in the last three decades as a major approach to discover new drugs . Our group is focused on the regulation of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), a conserved eukaryotic kinase that belongs to the DYRK family and the CMGC group, which includes cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSK), and Ccd2-like kinases (CLKs). Five years ago, a series of tricyclic aminopyrimidine derivatives was synthesized and evaluated on DYRK1A and DYRK1B. \u0000A fragment-growing approach was performed using a novel in silico tool that drills down through, to evaluate hundreds of thousands fragments extracted from co-crystallized kinase/inhibitor complexes. Addition of aromatic fragments on C2 seemed to increase the interaction with the hinge region. \u0000Efficient metal catalyzed C–H arylation of 8-alkyl-thiazolo[5,4-f]-quinazolin-9-ones was explored for SAR studies. Application of this powerful chemical tool at the last stage of the synthesis of kinase inhibitors allowed the synthesis of arrays of molecules inspired by fragment-growing studies generated by molecular modeling calculations. Among the potentially active compounds designed through this strategy, FC162 (Cc) exhibits nanomolar IC50 values against some kinases, and is the best candidate for development as a DYRK kinase inhibitor.","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":"80907866","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}

引用次数: 1