Synthesis and biological assessment of indole derivatives containing penta-heterocycles scaffold as novel anticancer agents towards A549 and K562 cells.

Herein, a new series of 2-chloro- N -(5-(2-oxoindolin-3-yl)-4 H -pyrazol-3-yl) acetamide derivatives containing 1,3,4 - thiadiazole ( 10a - i ) and 4 H -1,2,4-triazol-4-amine ( 11a - r ) moiety was designed, synthesised as novel anticancer agents. The antiproliferative activity values indicated that compound 10 b stood as the most potent derivative with IC 50 values of 12.0 nM and 10 nM against A549 and K562 cells, respectively. Mechanism investigation and docking studies of 10 b indicated that it possessed good apoptosis characteristic and dose-dependent growth arrest of A549 and K562 cells, blocked cell cycle into G2/M phase. Interestingly, 10 b suppressed the growth of A549 and K562 cells via modulation of EGFR and p53-MDM2 mediated pathway.