Bioorganic Chemistry (2020)
Update date:2022-08-16
Topics:
Abbass, Safinaz E. S.
Allam, Heba Abdelrasheed
Aly, Enayat E.
El Kerdawy, Ahmed M.
Farouk, Ahmed K. B. A. W.
Rashwan, Essam
The present study describes the synthesis of 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines starting from 4-chloro derivative VI via the reaction with either phenolic compounds to obtain VIIa-f, IXa-d, 2-amino-6-(un)substituted benzothiazole to produce VIIIa-c or hydrazine hydrate to give X. Reaction of the hydrazino functionality of X with appropriate acid anhydride, acid chloride or aldehyde affords XIa-c, XIIa-c and XIVa-i, respectively. The target compounds were screened for their efficacy as EGFR inhibitors compared to gefitinib. Compounds eliciting superior EGFR inhibitory activity were further screened for their in vitro cytotoxicity against two human cancer cell lines namely: MCF7 (breast) and A549 (lung), in addition to normal fibroblast cell WI38 relative to gefitinib as a reference. Furthermore, compounds that showed potent inhibitory activity on wild-type EGFR were screened against mutant EGFR and assayed for their cytotoxicity against mutant EGFR-expressing cell lines PC9 and HCC827. The unsubstituted benzothiazol-2-amine VIIa showing superior EGFR inhibition (IC50 = 0.096 μM) and anticancer activity against MCF-7 cell line (IC50 = 2.49 μM) was subjected to cell cycle analysis and apoptotic assay. Moreover, a molecular docking study was performed to investigate the interaction of some representive compounds with the active site of EGFR- TK.
View MoreJiYi Chemical (Beijing) Co., Ltd.
Contact:+86-10-89385733
Address:Shilou Town of Fangshan District, Beijing
Xi'an North Information Industry Co., Ltd. Weilv Chemical Department
Contact:+86-29-88156413
Address:Jixiang Road 99 Xi'an Shaanxi Province
SHANDONG QINGYUNCHANGXIN CHEMICAL SCIENCE-TECH CO.,LTD
Contact:86-21-60560171
Address:1689Donghuan Rade,Qingyun County, Dezhou City, Shandong,China
HANGZHOU YUNUO CHEMICAL CO.,LTD
website:http://www.yunuochem.com
Contact:0571-83715115
Address:hangzhou
Contact:027-87677569
Address:Room 2203, yujingmingmen Buidling One, xiongchu Road, wuhan city, hubei province, China
Doi:10.1007/s10973-018-7371-z
(2018)Doi:10.1007/BF01342330
(1936)Doi:10.1134/S1070363214010204
()Doi:10.1039/C39790000908
(1979)Doi:10.1021/j100368a013
(1990)Doi:10.1021/acs.orglett.1c00929
(2021)