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
{"title":"N-Acylhydrazone derivatives as potent histone deacetylase 6 inhibitors","authors":"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","doi":"10.3390/ecmc-4-05584","DOIUrl":"https://doi.org/10.3390/ecmc-4-05584","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90731470","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}
J. G. Carneiro, Cindy Magda Araújo dos Santos Freire, Marcelo Lopes Moreira, Manuela Araújo Carneiro, José Edvar Monteiro Júnior, José E. C. Freire
{"title":"In silico study of the polymyxin resistance in the genomes of Pseudomonas aeruginosa","authors":"J. G. Carneiro, Cindy Magda Araújo dos Santos Freire, Marcelo Lopes Moreira, Manuela Araújo Carneiro, José Edvar Monteiro Júnior, José E. C. Freire","doi":"10.3390/ecmc-4-05583","DOIUrl":"https://doi.org/10.3390/ecmc-4-05583","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82685637","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}
A. Spivak, R. Khalitova, D. Nedopekina, L. Dzhemileva, M. Yunusbaeva, V. Odinokov, V. D’yakonov, U. Dzhemilev
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).
{"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":"14 1","pages":""},"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}
Aleksandar Kočović, Miroslav Sovrlić, M. Tomovic, Jovana V Bradic, A. Petkovic
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.
{"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":"162 1","pages":""},"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}
C. Fernandes, Ye' Zaw Phyo, João Ribeiro, S. Cravo, M. Tiritan, Artur M. S. Silva, A. Kijjoa, M. Pinto
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]. From 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]. In 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. Acknowledgements: This 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. [1] Shagufta, A.I. Eur. J. Med. Chem., 2016, 116, 267-280. [2] Fernandes, C. et al. Bioorg. Med. Chem. 2014, 22, 1049-1062. [3] Fernandes, C. et al. Pharmaceuticals, 2017, 10, 50, doi:10.3390/ph10020050. [4] Phyo, Y.Z. et al. Molecules, 2018, 23, 142, doi:10.3390/molecules23010142. [5] Carraro, M.L. et al. Chirality, 2017, 1–10 [6] Fernandes, C. et al. Chirality, 2017, 29(8),430-442.
近年来，山酮衍生物一直是多项研究的核心，主要是由于其广泛的生物学和药理活性[1]。近年来，考虑到与生物活性相关的对映体选择性研究[2,3]以及液相色谱(LC)中手性固定相(CSPs)的选择剂[4,5]，口山酮(CDXs)的手性衍生物引起了人们的极大兴趣。从药物化学的角度来看，我们小组合成的一些cdx显示出有趣的生物活性[2,3]。除了作为新药的潜力外，CDXs还提供了有希望的LC对映体拆分结果[6]。在我们的研究中，我们合成了新的对映体纯cdx用于生物活性评价和新的csp的选择器，证实了cdx不仅在药物化学领域而且在分析应用中具有重要的应用。致谢:本研究得到了战略基金UID/Multi/04423/2013和UID/QUI/00062/2013的部分支持，通过FCT和ERDF提供的国家基金，在PT2020框架内，项目PTDC/MAR-BIO/4694/2014(参考文献poci -01-0145- federal -016790;项目编号3599-PPCDT);poci -01-0145-联邦-028736，由COMPETE 2020、葡萄牙2020和欧盟通过ERDF、FCT通过国家基金、葡萄牙核磁共振网络和CHIRALXANT-CESPU-2018共同资助。[1]张志强，张志强。医学化学。中文信息学报，2016,16(1):267-280。[2]张志强，张志强。Bioorg。医学化学，2014,22,1049-1062。[3]张志强，张志强。医药，2017,10,50,doi:10.3390/ph10020050。[4]刘永忠，刘永忠，等。分子学报，2018,23,142,doi:10.3390/molecules23010142。[5]张晓明，张晓明。李建军，张建军，等。手性研究进展[6]。手性，2017,29(8)，430-442。
{"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":"24 1","pages":""},"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}
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.
{"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":"30 1","pages":""},"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}
V. D’yakonov, L. Dzhemileva, R. A. Tuktarova, A. A. Makarov, Svetlana R. Ishmukhametova, E. Andreev, U. Dzhemilev
{"title":"Z-Stereoselective catalytic synthesis of natural acids, lembehynes, and acetogenins - Modern preparations for medicine","authors":"V. D’yakonov, L. Dzhemileva, R. A. Tuktarova, A. A. Makarov, Svetlana R. Ishmukhametova, E. Andreev, U. Dzhemilev","doi":"10.3390/ECMC-4-05613","DOIUrl":"https://doi.org/10.3390/ECMC-4-05613","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83047026","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}
C. Sewani-rusike, C. Tata, D. Ndinteh, B. Nkeh-Chungag, O. O. Oyedeji
{"title":"Effect of Senecio serratuloides and its bioactive compound on hypertension","authors":"C. Sewani-rusike, C. Tata, D. Ndinteh, B. Nkeh-Chungag, O. O. Oyedeji","doi":"10.3390/ecmc-4-05602","DOIUrl":"https://doi.org/10.3390/ecmc-4-05602","url":null,"abstract":"","PeriodicalId":20450,"journal":{"name":"Proceedings of 4th International Electronic Conference on Medicinal Chemistry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86440464","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}
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. Good 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.
{"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":"22 1","pages":""},"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}
Florence Couly, J. Diharce, P. Bonnet, M. Laurent, Corinne Fruit, T. Besson
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. A 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. Efficient 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.
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