Cyclic Marinopyrrole Derivatives as Disruptors of Mcl-1 and Bcl-xL Binding to Bim

Marine Drugs

Chunwei Cheng¹  Yan Liu³  Maria E. Balasis³  Nicholas L. Simmons²  Jerry Li³  Hao Song¹  Lili Pan¹  Yong Qin¹  K. C. Nicolaou²  Said M. Sebti³ 

[1] Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education and State Key Laboratory of Biotherapy, Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; E-Mails:;Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; E-Mail:;Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA; E-Mails:

关键词: cyclic marinopyrroles;    protein-protein interaction disruptors;    apoptosis;    SAR;   

DOI  :  10.3390/md12031335

来源: mdpi

【 摘 要 】

A series of novel cyclic marinopyrroles were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-x_L, was evaluated using ELISA assays. Both atropisomers of marinopyrrole A (1) show similar potency. A tetrabromo congener 9 is two-fold more potent than 1. Two novel cyclic marinopyrroles (3 and 4) are two- to seven-fold more potent than 1.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.