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Structure-based design of flavonoid compounds as a new class of small-molecule inhibitors of the anti-apoptotic Bcl-2 proteins.

ABSTRACT: Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-231 breast cancer cell line with an IC50 value of 110 nM and effectively induces apoptosis.

SUBMITTER: Tang G

PROVIDER: S-EPMC2527594 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Structure-based design of flavonoid compounds as a new class of small-molecule inhibitors of the anti-apoptotic Bcl-2 proteins.

Tang Guozhi G Ding Ke K Ding Ke K Nikolovska-Coleska Zaneta Z Yang Chao-Yie CY Qiu Su S Shangary Sanjeev S Wang Renxiao R Guo Jie J Gao Wei W Meagher Jennifer J Stuckey Jeanne J Krajewski Krzysztof K Jiang Sheng S Roller Peter P PP Wang Shaomeng S

Journal of medicinal chemistry 20070607 14

Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-231 breast cancer cell line with an IC50 value of 110 nM and effectively induces apoptosis. ...[more]

PMID: 17552510

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