In silico Molecular Docking and ADME Studies of 1,3,4-Thiadiazole Derivatives in Relation to in vitro PON1 Activity

摘要: Background Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins cell membranes against oxidative modification. Objective Based on antioxidative properties PON1 significance 1,3,4-thiadiazoles in pharmaceutical chemistry, herein we aimed to evaluate the potentials 1,3,4-thiadiazole derivatives as activators. Methods 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]acetophenone (1-18) were vitro evaluated for their activator effects which was purified using ammonium sulfate precipitation (60-80%) DEAE-Sephadex anion exchange chromatography. Molecular docking studies performed detection affinities all compounds active site PON1. Moreover, Absorption, Distribution, Metabolism Excretion (ADME) also silico predicted. In molecular ADME carried out according modules Schrodinger's Maestro modeling package. Results All compounds, particularly 10, 13 17, determined promising activators apart from compound 1, them detected Besides, results indicated that potential orally bioavailable drug-like molecules. Conclusion activators, 17 stand drug candidates further antioxidant these can be investigated therapeutic many disorders such atherosclerosis, diabetes mellitus, obesity, chronic liver inflammation more.