K. Kapadiya, K. Kavadia, V. Khedkar, P. Dholaria, A. Jivani, R. Khunt
{"title":"Synthesis of fluoro-rich pyrimidine-5-carbonitriles as antitubercular agents against H37Rv receptor","authors":"K. Kapadiya, K. Kavadia, V. Khedkar, P. Dholaria, A. Jivani, R. Khunt","doi":"10.1515/hc-2022-0010","DOIUrl":null,"url":null,"abstract":"Abstract The purpose of this study was to prepare various derivatives of 4-amino-2-(3-fluoro-5-(trifluoromethyl)phenyl)-6-arylpyrimidine-5-carbonitrile (6a–6h) using a three-step procedure. The derivatives were screened in vitro for activity against Mycobacterium tuberculosis strain H37Rv. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Eight compounds showed activity against Mtb H37Rv, and among them, 6f showed the best value of MIC, IC50 (53 μM) and IC90 (62 μM). Minimum bactericidal concentration of compound 6f was higher than its MIC and was more time-dependent than the concentration. Compound 6f was more active against M. tuberculosis H37Rv under low oxygen than metronidazole and did not show good potency in different treatments and non-tuberculous mycobacteria. Furthermore, a molecular docking study against mycobacterial enoyl-ACP reductase (InhA) could provide valuable insights into the plausible mechanism of action, which could set the theme for lead optimization. Graphical abstract","PeriodicalId":12914,"journal":{"name":"Heterocyclic Communications","volume":"28 1","pages":"75 - 83"},"PeriodicalIF":1.3000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heterocyclic Communications","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1515/hc-2022-0010","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 1
Abstract
Abstract The purpose of this study was to prepare various derivatives of 4-amino-2-(3-fluoro-5-(trifluoromethyl)phenyl)-6-arylpyrimidine-5-carbonitrile (6a–6h) using a three-step procedure. The derivatives were screened in vitro for activity against Mycobacterium tuberculosis strain H37Rv. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Eight compounds showed activity against Mtb H37Rv, and among them, 6f showed the best value of MIC, IC50 (53 μM) and IC90 (62 μM). Minimum bactericidal concentration of compound 6f was higher than its MIC and was more time-dependent than the concentration. Compound 6f was more active against M. tuberculosis H37Rv under low oxygen than metronidazole and did not show good potency in different treatments and non-tuberculous mycobacteria. Furthermore, a molecular docking study against mycobacterial enoyl-ACP reductase (InhA) could provide valuable insights into the plausible mechanism of action, which could set the theme for lead optimization. Graphical abstract
期刊介绍：
Heterocyclic Communications (HC) is a bimonthly, peer-reviewed journal publishing preliminary communications, research articles, and reviews on significant developments in all phases of heterocyclic chemistry, including general synthesis, natural products, computational analysis, considerable biological activity and inorganic ring systems. Clear presentation of experimental and computational data is strongly emphasized. Heterocyclic chemistry is a rapidly growing field. By some estimates original research papers in heterocyclic chemistry have increased to more than 60% of the current organic chemistry literature published. This explosive growth is even greater when considering heterocyclic research published in materials science, physical, biophysical, analytical, bioorganic, pharmaceutical, medicinal and natural products journals. There is a need, therefore, for a journal dedicated explicitly to heterocyclic chemistry and the properties of heterocyclic compounds.
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