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

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs are traditional medicines for the treatment of inflammation, yet associated with serious side effects. Hence, need discovering novel compounds valuable clinical benefits is great importance. In this study, 18 derivatives p-nitrophenyl hydrazones were docked against COX-2, 5-LOX, H+/K+ ATPase, followed by predicting their drug-likeness absorption, distribution, metabolism, excretion (ADME) properties. From 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), 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 ATPase. These less COX-2 selective than control (celecoxib). “Drug-likeness” analysis passed Lipinski's, Egan's, Veber's, Muegge's, Ghose's rules. The also Pfizer GSK rules, well golden triangle's rule identification metabolically stable drugs. pharmacokinetic profiles excellent, safe, compliant potential activity. results study can be used future optimization those better molecular interactions inflammation-effective inhibition.