Archiv der Pharmazie (Weinheim) 2012-03-01

Synthesis and acetylcholinesterase and butyrylcholinesterase inhibitory activities of 7-alkoxyl substituted indolizinoquinoline-5,12-dione derivatives.

Zu-Ping Wu, Xi-Wei Wu, Ting Shen, Yan-Ping Li, Xi Cheng, Lian-Quan Gu, Zhi-Shu Huang, Lin-Kun An

Index: Arch. Pharm. (Weinheim) 345(3) , 175-84, (2012)

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Abstract

A series of novel 7-alkoxyl substituted indolizinoquinoline-5,12-dione derivatives were synthesized. The cholinesterase inhibition assays indicated that most synthesized compounds exhibited good activity for acetylcholinesterase (AChE) and high selectivity index of AChE over butyrylcholinesterase (BuChE). Compound 12b exhibited the most potent AChE inhibitory activity with an IC(50) value of 0.068 µM and the highest selectivity index of 144. Kinetic study of AChE indicated that a mixed type of inhibition pattern existed for these indolizinoquinoline-5,12-dione derivatives. Molecular docking study indicated that compound 12b could bind to both the catalytically active site and the peripheral anionic site of AChE.Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.