title: Exploring new selective 3-benzylquinoxaline-based MAO-A inhibitors: design, synthesis, biological evaluation and docking studies.
abstract: In this investigation, we searched for novel MAO-A inhibitors using a 3-benzylquinoxaline scaffold based on our earlier findings. Series of N'-(3-benzylquinoxalin-2-yl)acetohydrazide, 4a, N'-(3-benzylquinoxalin-2-yl)benzohydrazide derivatives 4b-f, N'-[2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetyl]benzohydrazide derivatives 7a-d, (9H-fluoren-9-yl)methyl 1-[2-(2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetyl)-hydrazinyl]-2-ylcarbamate derivatives 8a-c, 2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)-N'-benzylidene acetohydrazide derivatives 9a-h, and ethyl 2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetate derivatives 10a-e were synthesized and evaluated in vitro as inhibitors of the two monoamine oxidase isoforms, MAO-A and MAO-B. Most of the compounds showed a selective MAO-A inhibitory activity in the nanomolar or low micromolar range. Compounds 4e and 9g were the most potent derivatives with high MAO-A selectivity and their molecular docking studies were performed in order to rationalize the obtained biological result.
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt.
authors.forename: Sherine N
authors.initials: SN
authors.lastname: Khattab
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt.
authors.forename: Shimaa A H
authors.initials: SA
authors.lastname: Abdel Moneim
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Bekhit
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt; Department of Chemistry, Rabigh College of Science and Art, King Abdulaziz University, Saudi Arabia.
authors.forename: Abdel Moneim
authors.initials: AM
authors.lastname: El Massry
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt.
authors.forename: Seham Y
authors.initials: SY
authors.lastname: Hassan
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt; Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, 11451 Riyadh, Saudi Arabia.
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Faham
authors.affiliation: Pharmacognosy and Pharmaceutical Chemistry Department, Pharmacy College, Taibah University, Al-Madinha Al-Munawaraha, Saudi Arabia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Hany Emary
authors.initials: HE
authors.lastname: Ali Ahmed
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt; Department of Chemistry, College of Science, Taibah University, Al-Madinha Al-Munawaraha, Saudi Arabia. Electronic address: adel.amer@alex-sci.edu.eg.
authors.forename: Adel
authors.initials: A
authors.lastname: Amer
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D008996:Monoamine Oxidase Inhibitors; D011810:Quinoxalines; D008995:Monoamine Oxidase
keywords: Amino acids; Monoamine oxidase; N-Aroylhydrazine; N′-Acetylaroylhydrazine; Quinoxalin-2(1H)-one; Schiff's base