New diphenyl-1H-pyrazoles were synthesized and screened for CDK2 inhibition where 8d, 9b, 9c, and 9e exhibited promising activity (IC₅₀ = 51.21, 41.36, 29.31, and 40.54 nM respectively) compared to R-Roscovitine (IC₅₀ = 43.25 nM). Furthermore, preliminary anti-proliferative activity screening of some selected compounds on 60 cancer cell lines was performed at the (NCI/USA). Compounds 8a-c displayed promising growth inhibitory activity (mean %GI; 73.74, 94.32 and 74.19, respectively). Additionally, they were further selected by the NCI for five-dose assay, exhibiting pronounced activity against almost the full panel (GI₅₀ ranges; 0.181–5.19, 1.07–4.12 and 1.07–4.82 µM, respectively) and (Full panel GI₅₀ (MG-MID); 2.838, 2.306 and 2.770 µM, respectively). Screening the synthesized compounds 8a-c for inhibition of CDK isoforms revealed that compound 8a exhibited nearly equal inhibition to all the tested CDK isoforms, while compound 8b inhibits CDK4/D1 preferentially than the other isoforms and compound 8c inhibits CDK1, CDK2 and CDK4 more than CDK7. Flow cytometry cell cycle assay of 8a-c on Non-small cell lung carcinoma (NSCL HOP-92) cell line revealed S phase arrest by 8a and G1/S phase arrest by 8b and 8c. Apoptotic induction in HOP-92 cell line was also observed upon treatment with compounds 8a-c. Docking to CDK2 ATP binding site revealed similar interactions as the co-crystallized ligand R-Roscovitine (PDB code; 3ddq). These findings present compounds 8a-c as promising anti-proliferative agents.

新二苯基-1- ħ -pyrazoles合成和其中筛选CDK2抑制8D，9B，9C，和9E显示出有希望的活性（IC ₅₀  = 51.21，41.36，29.31，40.54和分别纳米）相比ř -roscovitine（IC ₅₀  = 43.25 纳米）。此外，在 (NCI/USA) 对 60 种癌细胞系进行了一些选定化合物的初步抗增殖活性筛选。化合物8a-c显示出有希望的生长抑制活性（平均 %GI；分别为 73.74、94.32 和 74.19）。此外，它们被 NCI 进一步选择用于五剂量测定，对几乎全组（GI ₅₀范围；分别为 0.181–5.19、1.07–4.12 和 1.07–4.82 µM）和（全面板 GI ₅₀ (MG-MID)；分别为 2.838、2.306 和 2.770 µM ）。筛选合成的化合物8a-c对 CDK 异构体的抑制作用表明，化合物8a对所有测试的 CDK 异构体表现出几乎相同的抑制作用，而化合物8b对 CDK4/D1 的抑制作用高于其他异构体，化合物8c对 CDK1、CDK2 和 CDK4 的抑制作用超过CDK7。的流式细胞术细胞周期测定8A-C对非小细胞肺癌（NSCL HOP-92）细胞系揭示S期阻滞由图8a和G1 / S期阻滞8B和8c。在用化合物8a-c处理时也观察到HOP-92细胞系中的细胞凋亡诱导。与 CDK2 ATP 结合位点的对接揭示了与共结晶配体R - Roscovitine（PDB 代码；3ddq）类似的相互作用。这些发现表明化合物8a-c是有前景的抗增殖剂。