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-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis Regulatory Proteins / chemistry*
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Bcl-2-Like Protein 11
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Blotting, Western
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Breast Neoplasms / drug therapy
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Catalysis
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Enzyme-Linked Immunosorbent Assay
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Female
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Humans
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Indicators and Reagents
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Isomerism
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Magnetic Resonance Spectroscopy
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Marine Toxins / pharmacology*
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Membrane Proteins / chemistry*
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Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
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Protein Binding / drug effects
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Proto-Oncogene Proteins / chemistry*
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Pyrroles / chemical synthesis
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Pyrroles / chemistry*
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Pyrroles / pharmacology*
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Spectrophotometry, Ultraviolet
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Structure-Activity Relationship
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bcl-X Protein / metabolism*
Substances
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Indicators and Reagents
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MCL1 protein, human
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Marine Toxins
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Membrane Proteins
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins
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Pyrroles
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bcl-X Protein