Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effects of anti-cyclooxygenases (COX-1 and COX-2), structure activity relationship, molecular docking and in silico ADMET of some synthesized chalcones

Siddig Ibrahim Abdelwahab¹ , Mohammed Al-Mamary¹, Khaled Hassanein¹, Manal Mohamed Elhassan Taha², Abdullah Farasani^1,3, Hassan Alhazmi^2,4

¹Medical Research Centre, Jazan University, Jazan, Saudi Arabia; ²College of Pharmacy, Jazan University, Jazan, Saudi Arabia; ³College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; ⁴Toxicology and Substance Abuse Research Centre, Jazan University, Jazan, Saudi Arabia.

For correspondence:- Siddig Abdelwahab Email: sadiqa@jazanu.edu.sa Tel:+966506612390

Accepted: 13 October 2022 Published: 30 November 2022

Citation: Abdelwahab SI, Al-Mamary M, Hassanein K, Taha MM, Farasani A, Alhazmi H. Effects of anti-cyclooxygenases (COX-1 and COX-2), structure activity relationship, molecular docking and in silico ADMET of some synthesized chalcones. Trop J Pharm Res 2022; 21(11):2419-2427 doi: 10.4314/tjpr.v21i11.22

© 2022 The authors.
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Abstract

Purpose: To develop effective cancer chemopreventive and anti-inï¬‚ammatory agents, a series of chalcones were prepared by reacting suitable aromatic aldehyde with appropriate acetophenones.

Methods: Twenty-four synthesized chalcones (namely, 1 - 24) were assessed for their in vitro anti-cyclooxygenase-1 (COX-1) and anti-cyclooxygenase-2 (COX-2) activity in a COX catalyzed prostaglandin synthesis bioassay. Molecular docking was done to investigate the ligand-protein interactions, and selectivity on both enzymes. ADMET (absorption, distribution, metabolism, excretion, toxicity) modeling and software were also used.

Results: The compounds inhibited both COX-1 and COX-2. Two compounds (3 and 19) demonstrated more marked COX-2 inhibition than compound 1. Indomethacin as a standard anti-cyclooxygenase shows unselective inhibition of 81.44 ± 6.5 and 91 ± 9.5, respectively. The in silico data revealed that a chalcone skeleton with C=O at 4-position, C2–C3 double bond and OH at 5-position are necessary properties for anti-cyclooxygenase effects. It was also revealed that the propenone moiety comprises of an appropriate scaffold which proposes a new acyclic 1,3-diphenylprop-2-en-1-ones with selective anti-COX effects. A molecular modeling investigations where these chalcones 1, 3 and 19 were docked in the active site of COX-2 depicted that the p-CH3 substituent on the C-4- phenyl ring A are oriented in the vicinity of the COX-2 secondary pocket Phe381, Gly526, Tyr385 and Val349.

Conclusion: Based on the screening for oral bioavailability, in silico ADMET, and toxicity risk assessment, this study shows that these compounds could be a cornerstone for the development of new pharmaceuticals in the battle against COX-associated inflammatory disorders.

Keywords: Chalcones; cyclooxygenase enzymes: docking; in silico ADMET