Cheng , ChunweiLiu, YanBalasis, Maria E.Garner, Thomas P.Li, JerrySimmons, Nicholas L.Berndt, NorbertSong, HaoPan, LiliQin, YongNicolaou, K.C.Gavathiotis, EvripidisSebti , Said M.Li, Rongshi2014-08-292014-08-292014Cheng , Chunwei, Liu, Yan, Balasis, Maria E., et al.. "Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim." <i>Marine Drugs,</i> 12, (2014) MDPI: 4311-4325. http://dx.doi.org/10.3390/md12084311.https://hdl.handle.net/1911/77133A series of novel marinopyrroles with sulfide and sulphone spacers 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. Fluorescence-quenching (FQ) assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis) and inhibited cell proliferation.engThis is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).Journal articlemarinopyrrolesprotein-protein interaction disruptorsapoptosisSARhttp://dx.doi.org/10.3390/md12084311