Synthesis and evaluation of quinazoline amino acid derivatives as mono amine oxidase (MAO) inhibitors.
A series of quinazolinone amino acid ester and quinazolinone amino acid hydrazides were prepared under microwave irradiation as well as conventional condition. The microwave irradiation afforded the product in less reaction time, higher yield and purity. The structures of the synthesized compounds were confirmed by IR, NMR, and elemental analysis. The new synthesized compounds were studied for their monoamine oxidase inhibitory activity. They showed more selective inhibitory activity toward MAO-A than MAO-B. Compounds 7, 10, and 15 showed MAO-A inhibition activity (IC50=3.6×10(-9), 2.8×10(-9), 2.1×10(-9) M, respectively) comparable to that of the standard clorgyline (IC50=2.9×10(-9)M). 2-(2-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)acetohydrazide 15 showed selective MAO-A inhibition activity (SI=39524) superior to that of the standard clorgyline (SI=33793). The acute toxicity of the synthesized compounds was determined. In addition, computer-assisted simulated docking experiments were performed to rationalize the biological activity.
Department of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Ibrahimia, Alexandria 21321, Egypt. Electronic address: sh.n.khattab@gmail.com.
Sherine Nabil
SN
Khattab
Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt. Electronic address: nesreensaied@yahoo.com.
Nesreen Saied
NS
Haiba
Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt.
Ahmed Mosaad
AM
Asal
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt. Electronic address: adnbekhit@hotmail.com.
Adnan A
AA
Bekhit
Department of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Ibrahimia, Alexandria 21321, Egypt; Department of Applied Chemistry, Faculty of Applied Science, Taibah University, Saudi Arabia. Electronic address: adel.amer@alex-sci.edu.eg.
Adel
A
Amer
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Electronic address: hamdym01@yahoo.com.
Hamdy M
HM
Abdel-Rahman
Department of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Ibrahimia, Alexandria 21321, Egypt; Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: aymanel_faham@hotmail.com.
Ayman
A
El-Faham
D000284:Administration, Oral; D000596:Amino Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001923:Brain Chemistry; D002417:Cattle; D003010:Clorgyline / Q000494:pharmacology; D004952:Esters; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008872:Microwaves; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D012701:Serotonin / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000596:Amino Acids; D001596:Benzylamines; D004952:Esters; D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D011799:Quinazolines; D012701:Serotonin; C030796:benzylamine; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; D003010:Clorgyline
Amino acids; Isatoic anhydride; Monoamine oxidase; Quinazolinones