Structure-based Discovery of Multi-target Directed Anti-infammatoryp-nitrophenyl Hydrazones; Molecular docking, drug-likeness, in-silicopharmacokinetics, and toxicity studies

We designed novel p-nitrophenyl hydrazones as multi-target inhibitors of COX-2, 5-LOX, and H+/K+ ATPase in a bid to overcome side effects associated to NSAIDs and coxibs. Specifically, compounds 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)indicated promise as potent multi-target inhibitors of COX-2, 5-LOX, and H+/K+ ATPase with potential anti-inflammatory activity devoid of adverse effects of NSAIDs. Interactions with important amino acids which are key for ant-inflammatory activity and proton pump inhibition were noticed. All the compounds are less COX-2 selective compared to celecoxib. These compounds in addition have shown druglike physicochemical properties, passed Lipinski’s, Egan’s, Veber’s, Muegge’s and Ghose’s rules for druglike small molecules and orally bioavailable drugs. The compounds also passed golden triangle’s rule for potent and metabolically stable drugs. Also, these compounds passed Pfizer and GSK rules. The compounds also indicated excellent pharmacokinetic profiles complementing their potential anti-inflammatory activity with apparent safety profiles.

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APA

Babalola, S., Igie, N & Odeyemi, B (2022). Structure-based Discovery of Multi-target Directed Anti-infammatoryp-nitrophenyl Hydrazones; Molecular docking, drug-likeness, in-silicopharmacokinetics, and toxicity studies. Afribary. Retrieved from https://track.afribary.com/works/manuscript-r1

MLA 8th

Babalola, Sodeeq, et. al. "Structure-based Discovery of Multi-target Directed Anti-infammatoryp-nitrophenyl Hydrazones; Molecular docking, drug-likeness, in-silicopharmacokinetics, and toxicity studies" Afribary. Afribary, 14 Sep. 2022, https://track.afribary.com/works/manuscript-r1. Accessed 14 Nov. 2024.

MLA7

Babalola, Sodeeq, Nosakhare Igie and B Odeyemi . "Structure-based Discovery of Multi-target Directed Anti-infammatoryp-nitrophenyl Hydrazones; Molecular docking, drug-likeness, in-silicopharmacokinetics, and toxicity studies". Afribary, Afribary, 14 Sep. 2022. Web. 14 Nov. 2024. < https://track.afribary.com/works/manuscript-r1 >.

Chicago

Babalola, Sodeeq, Nosakhare Igie and B Odeyemi . "Structure-based Discovery of Multi-target Directed Anti-infammatoryp-nitrophenyl Hydrazones; Molecular docking, drug-likeness, in-silicopharmacokinetics, and toxicity studies" Afribary (2022). Accessed November 14, 2024. https://track.afribary.com/works/manuscript-r1

Document Details
By: Sodeeq Babalola Nosakhare Igie B Isaiah Odeyemi Field: Chemistry Type: Paper 37 PAGES (12790 WORDS) (docx)