TY - JOUR
T1 - Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure
AU - Chen, Liqiang
AU - Petrelli, Riccardo
AU - Gao, Guangyao
AU - Wilson, Daniel J.
AU - McLean, Garrett T.
AU - Jayaram, Hiremagalur N.
AU - Sham, Yuk Y.
AU - Pankiewicz, Krzysztof W.
PY - 2010/8/15
Y1 - 2010/8/15
N2 - 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.
AB - 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.
KW - Cancer therapy
KW - Cinnamic hydroxamic acid
KW - Drug resistance
KW - Dual inhibitor
KW - Histone deacetylase
KW - Inosine monophosphate dehydrogenase
UR - http://www.scopus.com/inward/record.url?scp=77955466735&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955466735&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2010.06.081
DO - 10.1016/j.bmc.2010.06.081
M3 - Article
C2 - 20650640
AN - SCOPUS:77955466735
SN - 0968-0896
VL - 18
SP - 5950
EP - 5964
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 16
ER -