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

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:

• 4-azaphenanthrene-3
• 10-dione
• multi-component reactions
• synthesis
• tetrahydrobenzo[b] pyran
• docking
• MM-GBSA

Acknowledgments

The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education and Qassim University, Saudi Arabia for funding this research work through the project number (QU-IF-02-03-27803). The authors also thank to Qassim University for technical support.

Disclosure statement

The authors declare no conflicts of interest.

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.

Additional information

Funding

The funders had no role in the design of the study; in the collection, analyses or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.