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

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.

journal_name

Bioorg Med Chem

authors

Chen L,Petrelli R,Gao G,Wilson DJ,McLean GT,Jayaram HN,Sham YY,Pankiewicz KW

doi

10.1016/j.bmc.2010.06.081

subject

Has Abstract

pub_date

2010-08-15 00:00:00

pages

5950-64

issue

16

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(10)00609-7

journal_volume

18

pub_type

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