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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(04): e250-e266
DOI: 10.1055/s-0042-1759688
Original Article

Molecular Docking, Drug-Likeness Analysis, In Silico Pharmacokinetics, and Toxicity Studies of p-Nitrophenyl Hydrazones as Anti-inflammatory Compounds against COX-2, 5-LOX, and H+/K+ ATPase

Sodeeq Babalola
1   Department of Pharmaceutical and Medicinal Chemistry, Ahmadu Bello University, Zaria, Nigeria
,
Nosakhare Igie
2   Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas, United States
,
Isaiah Odeyemi
2   Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas, United States
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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs are traditional medicines for the treatment of inflammation, yet associated with serious side effects. Hence, the need for discovering novel compounds with valuable clinical benefits is of great importance. In this study, 18 derivatives of p-nitrophenyl hydrazones were docked against COX-2, 5-LOX, and H+/K+ ATPase, followed by predicting their drug-likeness and absorption, distribution, metabolism, and excretion (ADME) properties. From the docking analysis, 1-(4-nitrophenyl)-2-[(3,4,5-trimethoxyphenyl)methylidene]hydrazine (3), 4-hydroxy-2-methyl-6-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]thiochroman-1,1-dioxide (6), 4-methoxy-2-methyl-6-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]thiochroman-1,1-dioxide (8), 2-methyl-6-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]-4-(trifluoromethyl)thiochroman-1,1-dioxide (11), 4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]benzenesulfonamide (13), 4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]-3-(trifluoromethyl)benzenesulfonamide (14), 5-methyl-6-{4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]phenyl}-2,3,4,5-tetrahydropyridazin-3-ol (16), and 5-methyl-6-{4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]phenyl}-4,5-dihydropyridazin-3(2H)-one (17) showed promise as potent multi-target inhibitors of COX-2, 5-LOX, and H+/K+ ATPase. These compounds are less COX-2 selective than the control (celecoxib). “Drug-likeness” analysis passed Lipinski's, Egan's, Veber's, Muegge's, and Ghose's rules. The compounds also passed Pfizer and GSK rules, as well as golden triangle's rule for identification of potent and metabolically stable drugs. The pharmacokinetic profiles of the compounds were excellent, safe, and compliant with their potential anti-inflammatory activity. The results of the study can be used for future optimization of those derivatives for better molecular interactions against COX-2, 5-LOX, and H+/K+ ATPase, and inflammation-effective inhibition.

Keywords

p-nitrophenyl hydrazones - anti-inflammatory - molecular docking - docking simulation - pharmacokinetics - drug-likeness

Supplementary Material



Publication History

Received: 09 June 2022

Accepted: 03 November 2022

Article published online:
27 December 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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