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Synthesis and proteasome inhibition of lithocholic acid derivatives.

ABSTRACT: A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic acid hemiester derivative (13) displayed the most potent proteasome inhibition with IC(50) = 1.9 ?M. Enzyme kinetic analysis indicates that these lithocholic acid derivatives are noncompetitive inhibitors of the proteasome.

SUBMITTER: Dang Z

PROVIDER: S-EPMC3072167 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Synthesis and proteasome inhibition of lithocholic acid derivatives.

Dang Zhao Z Lin Andrew A Ho Phong P Soroka Dominique D Lee Kuo-Hsiung KH Huang Li L Chen Chin-Ho CH

Bioorganic & medicinal chemistry letters 20110217 7

A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic acid hemiester derivative (13) displayed the most potent proteasome inhibition with IC(50) = 1.9 μM. Enzyme kinetic analysis indicates that these lithocholic acid derivatives are noncompetitive inhibitors of the proteas ...[more]

PMID: 21388808

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