Search for novel histone deacetylase inhibitors. Part II: design and synthesis of novel isoferulic acid derivatives.
Previously, we described the discovery of potent ferulic acid-based histone deacetylase inhibitors (HDACIs) with halogeno-acetanilide as novel surface recognition moiety (SRM). In order to improve the affinity and activity of these HDACIs, twenty seven isoferulic acid derivatives were described herein. The majority of title compounds displayed potent HDAC inhibitory activity. In particular, IF5 and IF6 exhibited significant enzymatic inhibitory activities, with IC50 values of 0.73 ± 0.08 and 0.57 ± 0.16 μM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against human cancer cells. Especially, IF6 displayed promising profile as an antitumor candidate with IC50 value of 3.91 ± 0.97 μM against HeLa cells. The results indicated that these isoferulic acid derivatives could serve as promising lead compounds for further optimization.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
Wen
W
Lu
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
Fang
F
Wang
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
Tao
T
Zhang
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
Jinyun
J
Dong
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
Hongping
H
Gao
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
Ping
P
Su
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China.
Yaling
Y
Shi
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, PR China. Electronic address: zhj8623@mail.xjtu.edu.cn.
Jie
J
Zhang
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015195:Drug Design; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation
D000970:Antineoplastic Agents; D002934:Cinnamates; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; C008180:isoferulic acid
Anticancer; HDAC inhibitor; Histone deacetylase; Isoferulic acid