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

Chunwei Cheng; Yan Liu; Maria E. Balasis; Nicholas L. Simmons; Jerry Li; Hao Song; Lili Pan; Yong Qin; K. C. Nicolaou; Said M. Sebti; Rongshi Li

doi:10.3390/md12031335

Marine Drugs (Mar 2014)

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

Chunwei Cheng,
Yan Liu,
Maria E. Balasis,
Nicholas L. Simmons,
Jerry Li,
Hao Song,
Lili Pan,
Yong Qin,
K. C. Nicolaou,
Said M. Sebti,
Rongshi Li

Affiliations

Chunwei Cheng: 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
Yan Liu: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
Maria E. Balasis: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
Nicholas L. Simmons: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Jerry Li: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
Hao Song: 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
Lili Pan: 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
Yong Qin: 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
K. C. Nicolaou: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Said M. Sebti: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
Rongshi Li: Chemical Biology & Molecular Medicine Program, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA

DOI: https://doi.org/10.3390/md12031335
Journal volume & issue: Vol. 12, no. 3
pp. 1335 – 1348

Abstract

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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-xL, 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.

Published in Marine Drugs

ISSN: 1660-3397 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/marinedrugs

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