Novel series of benzo[d]thiazolyl substituted-2-quinolone hybrids: Design, synthesis, biological evaluation and in-silico insights

A novel series of 3-(2-(4-(substituted-benzo[d]thiazol-2-yl)phenylamino)acetyl)-4-hydroxy-1-methyl/phenyl quinolin-2(1H)-one (7a-f and 8a-f) were synthesized. Reaction of appropriately substituted-2-(4-amino phenyl)benzo[d]thiazole (4a-f) with 3-(2-bromoacety1)-4-hydroxy-l-methyl/phenyl quinolin2(1H)-one (5/6) in the presence of glacial acetic acid resulted in desired compounds. Structures of the synthesized compounds were characterized based on their spectral (IR, H-1 NMR, C-13 NMR and MS) and elemental analysis. The cytotoxicity screening studies revealed that MCF-7 and WRL68 cancer cells were sensitive to all the tested compounds. Out of twelve novel hybrids, compound 8f displayed the most significant anticancer activity. Docking studies were performed in order to understand the binding mode of the title compounds at the active site of the target enzyme (EGFR tyrosine kinase, 1M17). Compounds 8f and 7f displayed prominent and conserved binding interactions against 1M17. In addition, compounds 7e, 7f, 8e, and 8f exhibited interesting in vitro antibacterial activity, especially against Gram-negative bacteria E. coli. In summary, the novel benzo[d]thiazolyl substituted-2-quinolone hybrid (8f) could be considered as promising hit and could be further exploited for developing potential anticancer/antimicrobial agents. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

A novel series of benzo[d]thiazolyl substituted-2-quinolone hybrids were synthesized, showing significant cytotoxicity against cancer cells, especially compound 8f. Docking studies revealed important binding interactions of compounds 8f and 7f with EGFR tyrosine kinase. Additionally, compounds 7e, 7f, 8e, and 8f exhibited antibacterial activity, particularly against E. coli.