The purpose of this study is to synthesize novel N,2,6-trisubstituted 1H-benzimidazole derivatives and evaluation of their antibacterial, antifungal, and anticancer activities as well as to study their mechanism of action.
Replacement of a key carboxylic acid in a dual MCL-1/BCL-xL inhibitor with bioisosteres was successful, and resulted in the discovery of an acylsulfonamide-derived compound (7d) with the greatest anti-leukemic activity of the entire series.
New pyrazolylindolin-2-one linked coumarin derivatives were designed as dual BRAFV600E/VEGFR-2 inhibitors targeting melanoma cells A375. Docking simulation showed various interactions with the binding residues in BRAFV600E and VEGFR-2 active sites.
Twenty 3-methylenamino-4(3H)-quinazolone derivatives were synthesized via imine formation. Compounds 5, 6, and 7 showed potent cytotoxicity against RD and MDA-MB-231, low toxicity to normal cells, and strong EGFR binding, with good ADMET profiles.
A series of novel dihydroorotate dehydrogenase (DHODH) inhibitors designated as N-pyridinyl ureidobenzenesulfonates (PYRUB-SOs) and their hydrochloride salts were designed, synthesized, and evaluated for their biological activity.