Unveiling cytotoxicity and antimicrobial potential of novel N-(2-((5-aryl-quinolin-8-yl)oxy)ethyl)sulfonamide derivatives: synthesis, cytotoxicity, antimicrobial, QSAR based anti-cancer evaluation and in silico studies.

The increased susceptibility of cancer patients towards devious infections due to immunosuppression is a cause of mortality worldwide and a major public health concern. The immunosuppression faced by the cancer patients and increasing susceptibility to infections necessitate the development of novel bioactive compounds with improved selectivity and reduced toxicity. In the present work, a series of N-(2-((5-(4-fluoro/methoxyphenyl)quinolin-8-yl)oxy)ethyl)sulfonamide, 9a-e N-(2-(2-((5-(4-fluorophenyl)quinolin-8-yl)oxy)ethoxy)ethyl)benzenesulfonamide 12a-f and N-(2-((5-(4-fluorophenyl)quinolin-8-yl)oxy)ethyl)substituted carboxamide, 13a-c derivatives have been synthesized. Out of the synthesized compounds, ten derivatives were evaluated for cytotoxicity for CDK 9 inhibition in human breast cancer cell lines MCF-7 and MDA-MB-231 and the human lung cancer cell line A-549. Compared with the reference drug Adriamycin, nine derivatives exhibited significant cytotoxic activity against the A-549 cell line, with GI50 values below 10 μg/mL. Against the MCF-7 cell line, compounds 9b, 9c, 10a, and 12a showed notable cytotoxicity. Furthermore, compounds 10a and 12a showed activity against the MDA-MB-231 cell line, suggesting broader anticancer potential. Additionally, the synthesized compounds were evaluated for in vitro antimicrobial activity against E. coli, P. mirabilis, B. subtilis, S. albus, A. niger, and C. albicans and some of the compounds showed good potential against these microbes. QSAR and molecular docking were performed to evaluate the anti-cancer activity as inhibitors against the CDK9 protein. Furthermore, compounds 9a and 9d showed the highest binding energy and were selected for the MD simulations, which showed that the latter complex may possess relatively higher interaction affinity.