Chemistry and biodiversity (2018)
Update date:2022-08-05
Topics:
Hieu, Doan Thanh
Anh, Duong Tien
Hai, Pham-The
Huong, Le-Thi-Thu
Park, Eun Jae
Choi, Jeong Eun
Kang, Jong Soon
Dung, Phan Thi Phuong
Han, Sang-Bae
Nam, Nguyen-Hai
In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a?–?4i, 6a?–?6i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g?–?4i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub-micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.
View MoreContact:86-28-61993785
Address:No.70-13-21, North Section, Erhuan
website:http://www.synchemie.com/
Contact:+86-574-87642758
Address:Room 901, Yinyi Bund Building, 132 Renmin Road
Shandong Xingshun New Material Co., Ltd.
website:http://www.sd-xingshun.com
Contact:+86-519-86461196/+86-519-86464994
Address:Middle of Luhua East Road, Dingtao District
SEA BRGIHT INDUSTRY CO.,LIMITED
Contact:0086 755 8622 3990
Address:Rm 17B3,GuangCaiXinTianDi Bldg,GuiMiao Rd,NanShan District,Shenzhen,China
website:http://www.josunpharma.com
Contact:+86-311-80715268 80766839
Address:No.39, Zhaiying Street, Shijaizhuang,Hebei,China
Doi:10.1016/j.bmc.2018.10.022
(2018)Doi:10.1002/adsc.201100951
(2012)Doi:10.1080/17415993.2019.1590581
(2019)Doi:10.1039/c2ob25500f
(2012)Doi:10.1007/BF00811466
(1991)Doi:10.1021/acs.joc.1c00646
(2021)