ABSTRACT

In the present study, a series of novel thiadiazole derivatives were synthesized, with the goal of developing more potent anti-inflammatory compounds with fewer side effects. As per the synthetic protocol, in the presence of triethylamine and dichloromethane, the designed 1,3,4-thiadiazole derivatives of biphenyl-4-yloxy acetic acid were synthesized by conjugating 5-substituted phenyl-1,3,4-thiadiazole -2- amines and biphenyl-4-yloxy acetic acid. The structures of all the novel compounds are defined and tested by the spectral analysis and screened with carrageenan-induced paw edema method for in-vivo antiinflammatory activity. In silico evaluation was also carried out by docking the engineered ligands on the COX-2 receptor to obtain further insight into the protein-ligand interactions. In addition to the anti-inflammatory activity, a form of writhing caused by acetic acid was used to screen the title compounds for analgesic activity. Compounds 3f (71%) with 2,6-dichlorophenyl substitution resulted in extraordinary anti-inflammatory activity that was found to be equipotent with the standard drug Indomethacin (69%). The 3c (69 %), 3j (67 %) and 3d (64 %) derivatives exhibited substantial behavior and the findings obtained are in agreement with the findings of molecular docking. In comparison to standard drug aspirin, derivatives 3f (73 %), 3c (64 %), 3j (67 %) produced significant analgesic activity. These findings reveal that 3f is a promising, anti-inflammatory, and analgesic pharmacophore. Keywords: Thiadiazole, Antiinflammatory activity, In Silico evaluation, Analgesic activity, biphenyl derivatives, Spectral analysis
Publication date: 01/02/21

https://ijbpas.com/pdf/2021/February/MS_IJBPAS_2021_5554.pdf

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https://doi.org/10.31032/IJBPAS/2021/10.2.5554