Design, synthesis and biological evaluation of 3-aryl-rhodanine benzoic acids as anti-apoptotic protein Bcl-2 inhibitors

  • Bioorg Med Chem Lett. 2015 Nov 15;25(22):5265-9. doi: 10.1016/j.bmcl.2015.09.051.
Huansheng Fu  1 ,  Xuben Hou  1 ,  Lei Wang  1 ,  Yanyan Dun  1 ,  Xinying Yang  1 ,  Hao Fang  2
Affiliations
  • 1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Rd, Ji'nan 250012, PR China.
  • 2. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Rd, Ji'nan 250012, PR China. Electronic address: [email protected].
PMID: 26421995 DOI: 10.1016/j.bmcl.2015.09.051
Abstract

A new class of 3-aryl-rhodanine benzoic acid derivatives were designed, synthesized, and evaluated for their inhibition activities against anti-apoptotic Bcl-2 proteins. The potent compounds 33 and 41 bound to Bcl-2 with submicromolar Ki values and had selectivities to Bcl-2/Mcl-1 over Bcl-xL. In addition, they exhibited obvious antiproliferative activities in three human tumor cell lines (MDA-MB-231, K562 and PC-3).

Keywords
Apoptosis; Bcl-2; Inhibitor; Rhodanine.