TY - JOUR
T1 - Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents
AU - Cai, Jin
AU - Wei, Hongtao
AU - Hong, Kwon Ho
AU - Wu, Xiaoqing
AU - Zong, Xi
AU - Cao, Meng
AU - Wang, Peng
AU - Li, Lushen
AU - Sun, Chunlong
AU - Chen, Bo
AU - Zhou, Gaoxing
AU - Chen, Junqing
AU - Ji, Min
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Abstract 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.
AB - Abstract 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.
KW - 2-Aminobenzamide
KW - Antiproliferative activity
KW - Docking simulation
KW - Histone deacetylases (HDAC)
KW - Hydroxamate
KW - Trifluoromethyl ketone
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U2 - 10.1016/j.bmc.2015.04.028
DO - 10.1016/j.bmc.2015.04.028
M3 - Article
C2 - 25953722
AN - SCOPUS:84937403780
VL - 23
SP - 3457
EP - 3471
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 13
M1 - 12240
ER -