Synthesis of fluoro-rich pyrimidine-5-carbonitriles as antitubercular agents against H37Rv receptor

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.

HAuCl4 Catalyzed and Dibenzyl amine Centered A3 coupling reaction: Synthesis, Spectroscopic Proofing and Anti‐microbial Efficacy

“…The synthesized crude 4 a-4 j were tested for their activity against various Gram-positive bacteria like Bacillus subtilis MTCC121, Staphylococcus aureus MTCC 96, staphylococcus MLS-16 MTCC2940, Micrococcus luteus MTCC2470 and Gram-negative bacteria like Escherichia coli MTCC739, Pseudomonas aeruginosa MTCC2453, Klebsiella planticola MTCC530 taking chloramphenicol as a positive control, and Candida albicans MTCC3017 strain used for anti-fungal strain using nystatin as the positive control (Table 3 and Figure 2). [27][28][29] Scheme 2. Plausible mechanism for the A 3 coupling reaction by Gold catalyst.…”