Design, Synthesis and Anticancer Activity Studies of Novel Indole Derivatives as Bcl-2/Mcl-1 dual inhibitors

Abstract

Abstract A series of novel indole derivatives were designed, synthesized and evaluated for the binding affinity of Bcl-2 family proteins and antiproliferative activity against three selected cancer cell lines (PC-3, Jurkat, and MDA-MB-231). The preliminary structure-activity relationship (SAR) for this indole scaffold was summarized. Among all the compounds, compound 9k showed the best inhibitory activity against Bcl-2 and Mcl-1 proteins with IC50 values of 7.63 µM and 1.53 µM, respectively, which is comparable to the positive control AT-101. The docking study of it with Bcl-2 and Mcl-1 proteins indicated that it could bind to the active pocket of them through Van der Waals forces, hydrogen bond, etc. However, the three compounds with good binding affinity of Bcl-2 protein exhibited weaker antitumor activity compared to AT-101, which need further modification.