Cyclic Marinopyrrole Derivatives as Disruptors of Mcl-1 and Bcl-xL Binding to Bim
Balasis, Maria E.
Simmons, Nicholas L.
Sebti, Said M.
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.
cyclic marinopyrroles; protein-protein interaction disruptors; apoptosis; SAR