Design, synthesis and preliminary biological evaluation of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives as novel histone deacetylase inhibitors.
A novel series of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives comprising N-hydroxybenzamide group as zinc-chelating moiety were designed, synthesized and evaluated for their ability to inhibit histone deacetylases. These compounds possessed inhibitory activity against the enzymes with IC(50) values as low as 4.0 microM. Among them, the thiophene substituted derivative 5j (IC(50)=0.3 microM) and benzo[d][1,3]dioxole derivative 5t (IC(50)=0.4 microM) exhibited good antiproliferative activity against the growth of human colon carcinoma cell line HCT116 and non-small cell lung cancer cell (NSCLC) line A549. In addition, they were found to potently induce cell-cycle arrest at G2 phase.
Jiao
Jie
J
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 250012 Ji'nan, Shandong, PR China.
Fang
Hao
H
Wang
Xuejian
X
Guan
Peng
P
Yuan
Yumei
Y
Xu
Wenfang
W
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry
D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D013876:Thiophenes; C037689:benzamide; D006655:Histone Deacetylases