Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure

Liqiang Chen; Riccardo Petrelli; Guangyao Gao; Daniel J. Wilson; Garrett T. McLean; Hiremagalur N. Jayaram; Yuk Y. Sham; Krzysztof W. Pankiewicz

doi:10.1016/j.bmc.2010.06.081

Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure

Liqiang Chen, Riccardo Petrelli, Guangyao Gao, Daniel J. Wilson, Garrett T. McLean, Hiremagalur N. Jayaram, Yuk Y. Sham, Krzysztof W. Pankiewicz

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

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Abstract

Small molecules that act on multiple biological targets have been proposed to combat the drug resistance commonly observed for cancer chemotherapy. By combining the structural features of known inhibitors of inosine monophosphate dehydrogense (IMPDH) and histone deacetylase (HDAC), dual inhibitors of IMPDH and HDAC based on the scaffold of cinnamic hydroxamic acid (CHA) have been designed, synthesized, and evaluated in biological assays. Key features, including the linker length, linker functionality, substitution position, and interacting groups, have been explored. Their individual contribution to the inhibitory activities against human IMPDH1 and IMPDH2 as well as HDAC has been assessed.

Original language	English (US)
Pages (from-to)	5950-5964
Number of pages	15
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2010.06.081
State	Published - Aug 15 2010

Keywords

Cancer therapy
Cinnamic hydroxamic acid
Drug resistance
Dual inhibitor
Histone deacetylase
Inosine monophosphate dehydrogenase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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AU - Gao, Guangyao

AU - Wilson, Daniel J.

AU - McLean, Garrett T.

AU - Jayaram, Hiremagalur N.

AU - Sham, Yuk Y.

AU - Pankiewicz, Krzysztof W.

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Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure

Abstract

Keywords

UN SDGs

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