Synthesis and biological evaluation of a novel pyrazolecarbothioamide derivative (DK115) inducing cell cycle arrest at the G1 phase in HCT116 human colon cancer cells

A novel compound, 5-(2,3-dimethoxyphenyl)-3-(1-hydroxynaphthalen-2-yl)-N-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (designated DK115) was synthesized, and its antitumor efficacy was assessed. Exposure of DK115 to HCT116 human colon cancer cells inhibited cellular proliferation and clonogenicity. DK115 induced cell cycle arrest at the G1 phase. DK115 downregulated cyclin D1 expression, whereas upregulated p53 and p21 expressions. DK115-induced p21 was not observed in HCT116 cells lacking the p53 gene (p53−/−), suggesting that DK115 induces p21 expression via p53. These data demonstrate that a novel synthetic DK115 compound may possess antitumor activity through the induction of tumor suppressor p53-mediated G1 cell cycle arrest.