Abstract

Design, synthesis, docking, QSAR, ADME studies and pharmacological evaluation of biphenyl-2-oxadiazoles as anti-inflammatory agents

Author(s): Sujit G. Bhansali and Vithal M. Kulkarni

Various 2-(4'-methylbiphenyl-2-yl)-5-aryl-1,3,4-oxadiazole analogues were designed by rational drug design methods. These were synthesized by conventional and microwave assisted methods. Structures of synthesized compounds were confirmed by IR, 1H-NMR, mass and elemental analysis. Compounds were further evaluated for analgesic and anti-inflammatory activity by in vivo models. The synthesized compound VMSB 2, VMSB 4, VMSB 6, VMSB 8, VMSB 11, VMSB 12 and VMSB 14 exhibited significant analgesic and anti-inflammatory activities comparable to standard drug. Also, these compounds showed little ulcerogenic effect compared to standard drug. Docking studies were carried out to understand the binding mode of designed compounds with the COX-2 enzyme. From the docking study, it was observed that ligands bind to the hydrophobic clamp formed by the residues Arg120, Tyr355, Tyr385 and Trp387 which play an important role for COX-2 inhibition. Further, a two dimensional quantitative structure-activity relationship (2D-QSAR) model was obtained using multiple linear regression (MLR) analysis. The pharmacokinetic parameters were calculated for the synthesized compounds and were found to be within the acceptable range defined for human use revealing their potential as possible drug-like compounds. Hence, the results obtained indicated that these compounds can serve as good leads for further modification and optimization.

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