Design, green synthesis and pharmacological evaluation of novel 5,6-diaryl-1,2,4-triazines bearing 3-morpholinoethylamine moiety as potential antithrombotic agents^*

<p>The aim of this research work was to investigate a series of novel 5,6-diaryl-1,2,4-triazines (<b>3a</b>–<b>3q</b>) containing 3-morpholinoethylamine side chain, and to address their antiplatelet activity by <i>in vitro, ex vivo</i> and <i>in vivo</i> methods. All compounds were synthesized by environment benign route and their structures were unambiguously confirmed by spectral data. Compounds (<b>3l</b>) and (<b>3m</b>) were confirmed by their single crystal X-ray structures. Out of all the synthesized compounds, 10 were found to be more potent <i>in vitro</i> than aspirin; six of them were found to be prominent in <i>ex vivo</i> assays and one compound (<b>3d</b>) was found to have the most promising antithrombotic profile <i>in vivo</i>. Moreover, compound (<b>3d</b>) demonstrated less ulcerogenicity in rats as compared to aspirin. The selectivity of the most promising compound (<b>3d</b>) for COX-1 and COX-2 enzymes was determined with the help of molecular docking studies and the results were correlated with the biological activity.</p

Discovery of novel N-methyl carbazole tethered rhodanine derivatives as direct inhibitors of Mycobacterium tuberculosis InhA

International audienceInhA (Enoyl-ACP reductase) plays a crucial role in the biosynthetic pathway of cell wall synthesis in Mycobacterium tuberculosis (Mtb). Isoniazid (INH) is an important firstline drug, which inhibits InhA. The rapid increase in resistance to INH and currently marketed drugs as well as emergence of MDR-TB and XDR-TB has complicated the diagnosis and treatment of Mtb with ever increasing threat to human kind. Herein, we report novel N-methyl carbazole derivatives as potential anti-TB compounds acting directly via InhA inhibition. All the synthesized final compounds were screened against Mtb virulent cell line H 37 Rv and investigated the InhA enzyme inhibition. Interestingly, compound 9e displayed promising inhibition (91%) at 50 µM concentration and IC 50 of 2.82 µM against InhA. To understand the ligand receptor interaction between compound 9e and InhA, molecular docking and molecular dynamics experiments were performed. The computational results were in agreement with the observed experimental data. Further, the cytotoxicity studies on mammalian cells revealed that all the compounds were safe