Chemical Biology and Drug Design p. 1115 - 1120 (2015)
Update date:2022-07-29
Topics:
Hameed, Abdul
Zehra, Syeda T.
Shah, Syed J. A.
Khan, Khalid M.
Alharthy, Rima D.
Furtmann, Norbert
Bajorath, Jürgen
Tahir, Muhammad N.
Iqbal, Jamshed
Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3-b]pyrazines (6a-6q) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3-b]pyrazines showed 3-(3′-nitrophenyl)pyrido[2,3-b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC50 values of 0.466 ± 0.121 and 1.89 ± 0.05 μm, respectively. The analogues 3-(3′-methylphenyl)pyrido[2,3-b]pyrazine 6c and 3-(3′-fluorophenyl)pyrido[2,3-b]pyrazine 6f were found to be selective inhibition for BChE with IC50 values of 0.583 ± 0.052 μm and AChE with IC50 value of 0.899 ± 0.10 μm, respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors. A series of pyrido[2,3-b]pyrazine (6a-6q) derivatives has been synthesized and evaluated for inhibitory activities against cholinesterases; acetylcholinesterase, and butyrylcholinesterase. Molecular docking of active compounds was also performed to suggest the putative binding modes with cholinesterases.
View MoreHangzhou GreenCo Science & Technology Co., Ltd.
Contact:86-571-88257303
Address:1713 Room,Jingui Building,Gudun Road,Xihu District,Hangzhou,China
Contact:+86-10-83993285
Address:Rm.1708, Haobai Tower, Building 6, No.50, North Road, West Third Ring, Haidian District, Beijing, China
TIANJIN DONGRUXIANG MINERALS MARKETING CO.,LTD(expird)
Contact:22-58516360
Address:tianjin
Shandong Ailitong New Material Co.,Ltd
Contact:+86-536-3226266
Address:zhongjia village, putong town , qingzhou city,Shandong Province,China
ShenZhen InnoSyn Biotech Co.,Ltd
website:http://www.innosyns.com
Contact:+86-755-28351685
Address:Floor 5 & 6, Building A1, HAIKEXING Strategic Innovative Industrial Park, 16 BaoShan Road, PingShan District
Doi:10.1002/chem.200601035
(2007)Doi:10.1016/j.bmcl.2006.09.063
(2007)Doi:10.1134/S1070428006050101
(2006)Doi:10.1021/om0609362
(2007)Doi:10.1021/jm00147a013
(1985)Doi:10.1016/j.mencom.2012.09.016
(2012)