Virtual screening, SAR, and discovery of 5‐(indole‐3‐yl)‐2‐[(2‐nitrophenyl)amino] [1,3,4]‐oxadiazole as a novel Bcl‐2 inhibitor

A new series of oxadiazoles were designed to act as inhibitors of the anti‐apoptotic Bcl‐2 protein. Virtual screening led to the discovery of new hits that interact with Bcl‐2 at the BH 3 binding pocket. Further study of the structure–activity relationship of the most active compound of the first series, compound 1 , led to the discovery of a novel oxadiazole analogue, compound 16j , that was a more potent small‐molecule inhibitor of Bcl‐2. 16j had good in vitro inhibitory activity with submicromolar IC 50 values in a metastatic human breast cancer cell line ( MDA ‐ MB ‐231) and a human cervical cancer cell line (HeLa). The antitumour effect of 16j is concomitant with its ability to bind to Bcl‐2 protein as shown by an enzyme‐linked immunosorbent assay ( IC 50 = 4.27 μ m ). Compound 16j has a great potential to develop into highly active anticancer agent.