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Cyclic Marinopyrrole Derivatives as Disruptors of Mcl-1 and Bcl-xL Binding to Bim |
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| Authors: | 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 |
| Abstract: | 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. |
| Keywords: | cyclic marinopyrroles protein-protein interaction disruptors apoptosis SAR |