Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents

被引：35

作者：

Cai, Jin ^{[1
]}

Wei, Hongtao ^{[2
]}

Hong, Kwon Ho ^{[3
,4
]}

Wu, Xiaoqing ^{[5
]}

Zong, Xi ^{[1
]}

Cao, Meng ^{[6
]}

Wang, Peng ^{[6
]}

Li, Lushen ^{[6
]}

Sun, Chunlong ^{[1
]}

Chen, Bo ^{[6
]}

Zhou, Gaoxing ^{[6
]}

Chen, Junqing ^{[1
]}

Ji, Min ^{[1
,6
,7
,8
]}

机构：

[1] Southeast Univ, Inst Pharmaceut Engn, Sch Chem & Chem Engn, Nanjing 210096, Jiangsu, Peoples R China

[2] Qingdao Agr Univ, Coll Chem & Pharmaceut Sci, Qingdao 266109, Peoples R China

[3] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55414 USA

[4] Univ Minnesota, Inst Therapeut Discovery & Dev, Minneapolis, MN 55414 USA

[5] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA

[6] Southeast Univ, Sch Biol Sci & Med Engn, Nanjing 210096, Jiangsu, Peoples R China

[7] Suzhou Key Lab Biomat & Technol, Suzhou 215123, Peoples R China

[8] Collaborat Innovat Ctr Suzhou Nano Sci & Technol, Suzhou 215123, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 13期

关键词：

Histone deacetylases (HDAC); Antiproliferative activity; Hydroxamate; 2-Aminobenzamide; Trifluoromethyl ketone; Docking simulation; ANTIPROLIFERATIVE ACTIVITY; DASATINIB DERIVATIVES; CRYSTAL-STRUCTURE; HYDROXAMIC ACID; BREAST-CANCER; HUMAN HDAC8; PHASE-II; IN-VITRO; ACETYLATION; TRANSCRIPTION;

D O I：

10.1016/j.bmc.2015.04.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl ketone analogues have been designed and synthesized. The synthesized compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against three human cancer cell lines including A549, NCI-H661, and U937. Most analogues exhibited higher antiproliferative activities against human acute myeloid leukemia cell U937 than the other two human lung cancer cell lines. Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms. Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these compounds might have potential as lead compounds for the development of anti-tumor drugs with HDACs inhibitory activities. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：3457 / 3471

页数：15

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