Monoamine oxidase A and B inhibiting effect and molecular modeling of some synthesized coumarin derivatives

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• 作者：Omaima M. Abdelhafez^a ; ^{ommryan@yahoo.com} ; Kamelia M. Amin^b ; Hamed I. Ali^c ; Mohamed M. Abdalla^d ; Rasha Z. Batran^a
• 关键词：MAO-A and B ; 7-Oxycoumarins ; Acetohydrazides ; Dioxopyrrolidines ; Molecular modeling
• 刊名：Neurochemistry International
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：62
• 期：2
• 页码：198-209
• 全文大小：1154 K

文摘

New series of bioactive 7-oxycoumarin derivatives were synthesized and tested for their in vitro and in vivo monoamine oxidase (MAO) A and B inhibitory effect. In vitro studies revealed exceptionally potent and selective MAO-A inhibitors with K_i values on a picomolar range. The acetohydrazide (3b) and the dioxopyrrolidine derivative (7b) showed the most potent in vitro and in vivo MAO inhibition activity. Moreover, molecular modeling study of the synthesized compounds into MAO-A (PDB: 2Z5X) and MAO-B (PDB: 2XFN) binding sites exhibited direct correlation between AutoDock binding affinity and % inhibition MAO-A (pM) and MAO-B (¦ÌM). In addition, the results of in vivo MAO inhibiting properties (ED₅₀) of the tested compounds revealed better direct correlation.