Design, Synthesis, and Biological Evaluation of Pyrazole Derivatives

In this in vitro study , a series of novel pyrazole derivatives were designed, synthesized, and evaluated against five human cancer cell lines ( PC 3, A549, HL 60, HCT 116, and SW 620) for their antiproliferative and p53‐ MDM 2 binding inhibitory activities. Although biological evaluations showed that this series of compounds possessed weak p53‐ MDM 2 inhibitory activities, most of them displayed moderate to potent antiproliferative activities against the tested cells lines. Compound 11c exhibited the best potency for MDM 2 ( FP ‐ IC 50 = 29.22 μ m ) and demonstrated antiproliferative activities in response to the five tested cell lines ( IC 50 = 4.09–16.82 μ m ). Compared with the positive control Nutlin‐1, there was enhanced antiproliferative activity to p53‐mutated or p53‐deficient cell lines ( SW 620, HL 60, and PC 3).