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 Emary Ali 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

Adel Amer^*, Abdelrahman H. Hegazi, Mohammed Khalil Alshekh, Hany Emary Ali Ahmed, Saied M. Soliman, Antonin Maniquet, Rona R. Ramsay

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 (3-methoxy-4-hydroxy)benzoyl 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.

Original language	English
Article number	200050
Number of pages	18
Journal	Royal Society Open Science
Volume	7
DOIs	https://doi.org/10.1098/rsos.200050
Publication status	Published - 22 Apr 2020

Keywords

Structure-activity relationships
Quinazoline analogues
Antidepressant
Monoamine oxidase inhibitors

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10.1098/rsos.200050Licence: CC BY

Amer-2020-Design-synthesis-molecular-RSOS-200050-CC
Copyright © 2020 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Final published version, 13.6 MBLicence: CC BY

Cite this

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

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 (3-methoxy-4-hydroxy)benzoyl 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 = "Structure-activity relationships, Quinazoline analogues, Antidepressant, Monoamine oxidase inhibitors",

author = "Adel Amer and Hegazi, {Abdelrahman H.} and Alshekh, {Mohammed Khalil} and Ahmed, {Hany Emary Ali} and Soliman, {Saied M.} and Antonin Maniquet and Ramsay, {Rona R.}",

note = "Funding: Deanship of Scientific Research at Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia (project # 7101).",

year = "2020",

month = apr,

day = "22",

doi = "10.1098/rsos.200050",

language = "English",

volume = "7",

journal = "Royal Society Open Science",

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TY - JOUR

T1 - Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

AU - Amer, Adel

AU - Hegazi, Abdelrahman H.

AU - Alshekh, Mohammed Khalil

AU - Ahmed, Hany Emary Ali

AU - Soliman, Saied M.

AU - Maniquet, Antonin

AU - Ramsay, Rona R.

N1 - Funding: Deanship of Scientific Research at Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia (project # 7101).

PY - 2020/4/22

Y1 - 2020/4/22

N2 - 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 (3-methoxy-4-hydroxy)benzoyl 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.

AB - 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 (3-methoxy-4-hydroxy)benzoyl 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.

KW - Structure-activity relationships

KW - Quinazoline analogues

KW - Antidepressant

KW - Monoamine oxidase inhibitors

U2 - 10.1098/rsos.200050

DO - 10.1098/rsos.200050

M3 - Article

SN - 2054-5703

VL - 7

JO - Royal Society Open Science

JF - Royal Society Open Science

M1 - 200050

ER -

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

Abstract

Keywords

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