A series of novel 1,3,4-trisubstituted pyrazole derivatives were synthesized and evaluated for their cytotoxic activity against three different cancer cell lines namely HCT116, UO-31 and HepG2. Compounds 3b, 3d, 7b and 9 showed excellent anticancer activity against all the tested cancer cell lines and had better cytotoxic activities than the reference drug, Sorafenib. Therefore, these compounds were chosen to be further evaluated in a panel of HCC cell lines. Among them, 3b and 7b were the most active compounds against HCC cells used here. Further studies on the mechanism demonstrated that 3b and 7b induced apoptosis in addition to induction of cell cycle arrest at G2/M phase in HepG2 and Huh7 cells. Consistent with these results, caspase-3 assay was done and the results revealed that the pro-apoptotic activity of the target compounds could be due to the stimulation of caspases-3. In addition, CDK1 inhibition assay was done and it was found that compounds 3b and 7b inhibited CDK1 activities with IC₅₀ values of 2.38 and 1.52 µM, respectively. Finally, pyrazole derivatives 3b and 7b showed potent bioactivities, indicating that these compounds could be potent anticancer drugs in the future.

合成了一系列新颖的1,3,4-三取代的吡唑衍生物，并评估了它们对三种不同癌细胞系HCT116，UO-31和HepG2的细胞毒活性。与参考药物索拉非尼相比，化合物3b，3d，7b和9对所有测试的癌细胞系均显示出优异的抗癌活性，并具有更好的细胞毒活性。因此，选择这些化合物以在一组HCC细胞系中进一步评估。其中，3b和7b是针对此处使用的HCC细胞最具活性的化合物。对该机制的进一步研究表明3b和7b除了诱导HepG2和Huh7细胞的G2 / M期细胞周期停滞外，还诱导细胞凋亡。与这些结果一致，进行了caspase-3测定，结果表明目标化合物的促凋亡活性可能是由于caspases-3的刺激所致。此外，进行了CDK1抑制试验，发现化合物3b和7b抑制CDK1活性，IC ₅₀值分别为2.38和1.52 µM。最后，吡唑衍生物3b和7b显示出有效的生物活性，表明这些化合物将来可能是有效的抗癌药。