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

Donia Ben Salah; Ahlem Chakchouk-Mtibaa; Lotfi Mellouli; Houcine Ghalla; Waleed Koko; Sadeq M Al-Hazmy; Lamjed Mansour; Jameel Al-Tamimi; Najet Aouled Dlala; Younes Bouazizi; Khaireddine Dridi; Naceur Hamdi

doi:10.1080/07391102.2022.2114938

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

J Biomol Struct Dyn. 2022 Sep 9:1-17. doi: 10.1080/07391102.2022.2114938. Online ahead of print.

Authors

Affiliations

¹ Research Laboratory of Environmental Sciences and Technologies (LR16ES09), Higher Institute of Environmental Sciences and Technology, University of Carthage, Hammam-Lif, Tunisia.
² Laboratory of Microorganisms and Enzymatic Biotechnology and Biomolecules, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
³ Quantum and Statistical Physics Laboratory, University of Monastir, Monastir, Tunisia.
⁴ Department of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass, Saudi Arabia.
⁵ Chemistry Department, College of Science, Qassim University, Buraidah, Saudi Arabia.
⁶ Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁷ Chemistry Department, Jazan University, Jazan, Saudi Arabia.
⁸ Department of Chemistry, College of Science and Arts, QassimUniversity, Ar Rass, Saudi Arabia.

PMID: 36082583
DOI: 10.1080/07391102.2022.2114938

Abstract

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, ¹H NMR, ¹³C 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.

Keywords: 10-dione; 4-azaphenanthrene-3; MM-GBSA; docking; multi-component reactions; synthesis; tetrahydrobenzo[b] pyran.