Synthesis, antimicrobial and antioxidant activity of triazole, pyrazole containing thiazole derivatives and molecular docking studies on COVID-19.

New series of biologically active triazole and pyrazole compounds containing 2, 4-disubstituted thiazole analogues (12a-l) were synthesized from p-hydroxy benzaldehyde and phenyl hydrazine in excellent yields and purity. All the synthesized compounds were unambiguously identified based on their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS). The final derivatives were evaluated for their in vitro anti-microbial activity after thorough purification. Among all the tested compounds, the compound 12e, 12f and 12 k possess the highest growth inhibitory activity at MIC values of 4.8, 5.1 and 4.0 µg/ml respectively. The antioxidant properties of these compounds demonstrated and revealed remarkable activity compared to the standard antioxidant by using the DPPH free radical-scavenging assay. Moreover, molecular docking studies to evaluate the probable interactions with the catalytic domain of the gram-positive S. aureus topoisomerase IV enzyme may provide new insights for developing these new hybrids as potential antimicrobial agents. The binding affinities of compounds 12a-l were ranging from - 10.0 to - 11.0 kcal/mol with topoisomerase IV enzyme and with COVID-19 main protease binding affinities are ranging from - 8.2 to - 9.3 kcal/mol. These docking studies reveal that the compounds 12a-l could be the best inhibitors for the novel SARS Cov-2 virus and have more future in discovery of potent drug candidates.

Synthesis of tert-butyl (substituted benzamido)phenylcarbamate derivatives: anti-inflammatory activity and docking studies.

A series of new tert-butyl 2-(substituted benzamido) phenylcarbamate (4a-4j) were synthesized by the condensation of tert-butyl 2-amino phenylcarbamate (3) with various substituted carboxylic acid in the presence of EDCI and HOBt as coupling reagent, obtain in excellent yields. The structures of all newly synthesized compounds were characterized spectroscopically and evaluated for in vivo anti-inflammatory activity compared to the standard drug, indomethacin, by using the carrageenan-induced rat paw edema protocol. Most of the compounds exhibited a promising anti-inflammatory activity within 9 to 12 h, the percentage of inhibition values ranging from 54.239 to 39.021%. The results revealed that the compounds 4i and 4a exhibited better or equivalent anti-inflammatory activity with the percentage of inhibition of 54.239 and 54.130%, respectively, which was comparable to standard drug. In addition to experimental results, in silico docking studies was used as a tool to verify and expand the experimental outcomes.