Cyclic marinopyrrole derivatives as disruptors of Mcl-1 and Bcl-x(L) binding to Bim

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 tetrabr...

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Veröffentlicht in:	Marine drugs 2014-03, Vol.12 (3), p.1335
Hauptverfasser:	Cheng, Chunwei, Liu, Yan, Balasis, Maria E, Simmons, Nicholas L, Li, Jerry, Song, Hao, Pan, Lili, Qin, Yong, Nicolaou, K C, Sebti, Said M, Li, Rongshi
Format:	Artikel
Sprache:	eng
Schlagworte:	Apoptosis - drug effects Apoptosis Regulatory Proteins - chemistry Bcl-2-Like Protein 11 bcl-X Protein - metabolism Blotting, Western Breast Neoplasms - drug therapy Catalysis Cell Line, Tumor Drug Screening Assays, Antitumor Enzyme-Linked Immunosorbent Assay Female Humans Indicators and Reagents Isomerism Magnetic Resonance Spectroscopy Marine Toxins - pharmacology Membrane Proteins - chemistry Myeloid Cell Leukemia Sequence 1 Protein - metabolism Protein Binding - drug effects Proto-Oncogene Proteins - chemistry Pyrroles - chemical synthesis Pyrroles - chemistry Pyrroles - pharmacology Spectrophotometry, Ultraviolet Structure-Activity Relationship
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Zusammenfassung:	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.
ISSN:	1660-3397
DOI:	10.3390/md12031335