Synthesis, Docking, Antioxidant, Antihyperlipidemic, Antiplatelet, Anticoagulant, and Vasodilatory Activities of Isoxazole Newly Synthesized Derivative

We synthesized isoxazole derivative: 4-({4-(dimethylamino) phenyl}methylidene)-3-methyl-1,2-isoxazole-5(4H)-one (PMX-5), characterized by FTIR, H-1-NMR and C-13-NMR. In computational analysis, PMX-5 showed high affinity for farnesoid X receptor, glycoprotein-VI, vitamin-K epoxide reductase, and guanylyl cyclase. At concentrations of 1, 3, 10, 100, 300, 700, and 1000 mu g/mL, it exhibited free radical scavenging effect as 3.2743 +/- 0.48, 10.8036 +/- 2.79, 15.2931 +/- 3.38, 29.6991 +/- 0.08, 37.2992 +/-.59, 47.4319 +/- 0.51, and 63.5001 +/- 1.23%, respectively. In high fat diet-induced hyperlipidemia, PMX-5 lowered total cholesterol, triglyceride, low-density lipoprotein, and very low-density lipoprotein levels, while elevated high-density lipoprotein levels significantly (p < 0.001 vs. saline) in rats. PMX-5 suppressed arachidonic acid and adenosine diphosphate-induced platelet aggregation with IC50 values of 192 and 831 mu M, respectively. It also showed anticoagulant potential by increasing plasma recalcification time to 101.2 +/- 2.4 s at 30 mu M, 108 +/- 2.2 s at 100 mu M, 132.2 +/- 2.9 and 202.4 +/- 4.6 s (p < 0.001) at 300 and 1000 mu M, respectively. PMX-5 partly relaxed phenylephrine and K+ (80 mM)-induced contractions in isolated rat aortic tissues. Thus, the current study reports the synthesis of PMX-5 and its pharmacological potentials.