Synthesis of novel antioxidant and antitumor 5-aminopyrazole derivatives, 2D/3D QSAR, and molecular docking.

5-Aminopyrazole serves as a vital precursor for several biologically active pyrazoloazines, including pyrazolopyridine, pyrazolopyrimidine, and pyrazolotriazine, as well as Schiff bases, thiourea, and phthalimide derivatives. In this study, we structurally characterized novel pyrazole derivatives by spectral IR, 1H and 13C NMR, and MASS spectroscopy. We also evaluated antioxidant activity of various derivatives using ABTS and DPPH methods and cytotoxicity in the hepatocellular carcinoma Hep-G2 cells by SRB assay. The most potent antitumor molecules were 5-aminopyrazole derivative 3, chloroacetanilide derivative 8, maleimide derivative 10a, pyrazolopyrimidine 16, and enamine 19, with IC50 values of 41, 3.6, 37, 24.4, and 17.7 μM, respectively. Complementary computational studies predicted QSAR and bioactivity of these molecules. Interestingly, the most effective compounds were also predicted to be kinase inhibitors; in addition, molecular docking with liver receptors (3MBG, 4XCU, and 4G9C) predicted promising interactions.