A novel group of indolyl‐1,2,4‐triazole‐chalcone hybrids was designed, synthesized,
and assessed for their anticancer activity. The synthesized compounds exhibited
significant antiproliferative activity. Compounds 9a and 9e exhibited significant
cancer inhibition with GI50 ranging from 3.69 to 20.40 μM and from 0.29 to
>100 μM, respectively. Both compounds displayed a broad spectrum of anticancer
activity with selectivity ratios ranging between 0.50–2.78 and 0.25–2.81 at the
GI50 level, respectively. The synthesized compounds were also screened for their
cytotoxicity by 3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazol (MTT) assay and
for inhibition of epidermal growth factor receptor (EGFR) and c‐MET (mesenchymalepithelial
transition factor). Some of the tested compounds exhibited significant
inhibition against EGFR and/or c‐MET. Compound 9b showed the highest c‐MET
inhibition (IC50 = 4.70 nM) compared to foretinib (IC50 = 2.5 nM). Compound 9d
showed equipotent activity compared with erlotinib against EGFR (IC50 = 0.052 μM)
and displayed significant c‐MET inhibition with an IC50 value of 4.90 nM.