Novel 3-phenyl-1- (alkylphenyl)-9-oxa-4-azaphenanthren-10-ones as inhibitors of some enzymes: synthesis, characterization, biological evaluation and molecular docking studies

• Published in: Journal of biomolecular structure & dynamics 2022-09, Vol.ahead-of-print (ahead-of-print), p.1-17
• Main Authors: Salah, Donia Ben, Chakchouk-Mtibaa, Ahlem, Mellouli, Lotfi, Ghalla, Houcine, Koko, Waleed, Al-Hazmy, Sadeq M., Mansour, Lamjed, Al-Tamimi, Jameel, Dlala, Najet Aouled, Bouazizi, Younes, Dridi, Khaireddine, Hamdi, Naceur
• Format: Article
• Language: English
• Subjects: 10-dione; 4-azaphenanthrene-3; docking; MM-GBSA; multi-component reactions; synthesis; tetrahydrobenzo[b] pyran
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2022.2114938

A series of novel 3-phenyl-1-(alkylphenyl)-9-oxa-4-azaphenanthren-10-ones and (E)-1-phenyl-3-(aryl)prop-2-en-1-ones were synthesized and characterized by IR, 1 H NMR, 13 C spectroscopy and elemental analysis. The synthesized Compounds 5a-f were subjected to molecular docking simulation with three proteins, namely, tyrosyl-tRNA synthetase, heme oxygenase 1 and acetylcholinesterase to evaluate the antibacterial, antioxidant and acetylcholinesterase inhibition, respectively. Moreover, the docked poses of all compounds inside the proteins were subjected to further dynamic simulation through the calculation of the binding free energy using MM-GBSA analysis. Compound 5d exhibits high potential inhibition against antibacterial, antioxidant and acetylcholinesterase activities. Compounds 3d, 3f, 5a and 5d recorded an important scavenging activity in DPPH and ABTS assays. Investigation of the anti-acetylcholinesterase activity of the synthesized compounds showed that Compounds 5a and 3d are the most potent inhibitors against AchE, with percent inhibition values of 38 and 30%, respectively. Communicated by Ramaswamy H. Sarma