Abstract
A new class of 3-aryl-rhodanine benzoic acid derivatives were designed, synthesized, and evaluated for their inhibition activities against anti-apoptotic Bcl-2 proteins. The potent compounds 33 and 41 bound to Bcl-2 with submicromolar Ki values and had selectivities to Bcl-2/Mcl-1 over Bcl-xL. In addition, they exhibited obvious antiproliferative activities in three human tumor cell lines (MDA-MB-231, K562 and PC-3).
Keywords:
Apoptosis; Bcl-2; Inhibitor; Rhodanine.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Benzoates / chemical synthesis
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Benzoates / pharmacology*
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Cell Line, Tumor
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Humans
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Molecular Docking Simulation
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Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
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Proto-Oncogene Proteins c-bcl-2 / ultrastructure
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Rhodanine / analogs & derivatives*
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Rhodanine / chemical synthesis
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Rhodanine / pharmacology
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Sulfonamides / pharmacology
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Thiazoles / pharmacology
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bcl-X Protein / antagonists & inhibitors
Substances
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Antineoplastic Agents
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BCL2 protein, human
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BCL2L1 protein, human
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Benzoates
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MCL1 protein, human
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins c-bcl-2
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Sulfonamides
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Thiazoles
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WL 276
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bcl-X Protein
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Rhodanine