Chemistry Department, Faculty of Science, Mansoura University, 25 El Gomhouria St, Mansoura, Dakahlia Governorate, 35516, Egypt.
Mol Divers. 2022 Apr;26(2):781-800. doi: 10.1007/s11030-021-10184-9. Epub 2021 Mar 8.
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, H and C 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 IC 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.
5-氨基吡唑是几种生物活性吡唑嗪类化合物的重要前体，包括吡唑并吡啶、吡唑并嘧啶和吡唑并三嗪，以及席夫碱、硫脲和邻苯二甲酰亚胺衍生物。在这项研究中，我们通过光谱 IR、H 和 C NMR 以及质谱对新型吡唑衍生物进行了结构表征。我们还使用 ABTS 和 DPPH 方法评估了各种衍生物的抗氧化活性，并通过 SRB 测定法评估了它们在肝癌 Hep-G2 细胞中的细胞毒性。最有效的抗肿瘤分子是 5-氨基吡唑衍生物 3、氯乙酰胺衍生物 8、马来酰亚胺衍生物 10a、吡唑并嘧啶 16 和烯胺 19，其 IC 值分别为 41、3.6、37、24.4 和 17.7 μM。补充计算研究预测了这些分子的 QSAR 和生物活性。有趣的是，预测最有效的化合物也是激酶抑制剂；此外，与肝脏受体（3MBG、4XCU 和 4G9C）的分子对接预测了有前途的相互作用。
