Efficient Synthesis and in Silico Studies of the Benzimidazole HybridScaffold with the Quinolinyloxadiazole Skeleton with Potentialα?Glucosidase Inhibitory, Anticoagulant, and Antiplatelet Activitiesfor Type-II Diabetes Mellitus Management and Treating ThromboticDisorders

摘要

The current study evaluates antidiabetic, anticoagulant,and antiplatelet activity of novel benzimidazole-containing quinolinyloxadiazoles. These derivatives are synthesized and characterized usingspectroscopy (FT-IR, 1H NMR, and mass spectroscopy) and singlecrystal X-ray diffraction methods. The inhibitory effects of thesecompounds were evaluated by the α-glucosidase inhibitory assay andshows the activity in the range of IC50 = 0.66 ± 0.05 to 3.79 ± 0.46μg/mL. In addition, molecular docking studies revealed thatbenzimidazole-containing quinolinyl oxadiazoles can correctly dockinto the target receptor protein of the human intestinal α-glucosidase,while their bioavailability/drug-likeness was predicted to be acceptablebut requires further optimization. On the other hand, compound 8aand 8d showed anticoagulant activity as they enhanced the clottingtime from control 180?410 and 180?390 s, respectively, in plateletrich plasma and 230?460 and 230?545 s in platelet poor plasma. Furthermore, only 8a showed antiplatelet activity byinhibiting epinephrine-induced platelet aggregation, and the observed aggregation inhibition was found to be 93.4%.Compounds 8a?f show nontoxic properties because of the non-hydrolyzing properties in the RBC cells. In addition, 8a and 8dshow anti-edema and anti-hemorrhagic properties in the experimental mice. These findings reveal that benzimidazolecontaining quinolinyl oxadiazoles act as α-glucosidase inhibitors to develop novel therapeutics for treating type-II diabetesmellitus and can act as lead molecules in drug discovery as potential antidiabetic and antithrombotic agents.