Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

Adel Amer; Abdelrahman H Hegazi; Mohammed Khalil Alshekh; Hany E A Ahmed; Saied M Soliman; Antonin Maniquet; Rona R Ramsay

doi:10.1098/rsos.200050

Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

R Soc Open Sci. 2020 Apr 22;7(4):200050. doi: 10.1098/rsos.200050. eCollection 2020 Apr.

Authors

Adel Amer^{1

2}, Abdelrahman H Hegazi², Mohammed Khalil Alshekh¹, Hany E A Ahmed^{3

4}, Saied M Soliman², Antonin Maniquet⁵, Rona R Ramsay⁵

Affiliations

¹ Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.
² Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt.
³ Pharmacognosy and Pharmaceutical Chemistry Department, Pharmacy College, Taibah University, Al-Madinha Al-Munawarah, Saudi Arabia.
⁴ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
⁵ Biomedical Sciences Research Complex, University of St Andrews, Biomolecular Sciences Building, North Haugh, St Andrews KY16 9ST, UK.

Abstract

A new series of N'-substituted benzylidene-2-(4-oxo-2-phenyl-1,4-dihydroquinazolin-3(2H)-yl)acetohydrazide (5a-5h) has been synthesized, characterized by FT-IR, NMR spectroscopy and mass spectrometry and tested against human monoamine oxidase (MAO) A and B. Only (4-hydroxy-3-methoxybenzylidene) substituted compounds gave submicromolar inhibition of MAO-A and MAO-B. Changing the phenyl substituent to methyl on the unsaturated quinazoline ring (12a-12d) decreased inhibition, but a less flexible linker (14a-14d) resulted in selective micromolar inhibition of hMAO-B providing insight for ongoing design.

Keywords: antidepressant; monoamine oxidase inhibitors; quinazoline analogues; structure–activity relationships.

Associated data

figshare/10.6084/m9.figshare.c.4929348