Structure-Activity-Relationship Study of the Novel p21/waf1 Inhibitor for Anti-Cancer Agents against Renal Cell Carcinoma

The p21/waf1, especially cytoplasmic or phosphorylated p21/waf1, is one of cancer prognostic marker and known to have the anti-apoptotic function in renal cell carcinoma. Thus, it would be a good therapeutic option to impair the anti-apoptotic activity of p21/waf1 in renal cell carcinoma by small molecule inhibitors. In this study, we are trying to find more potent small molecule inhibitors derived from the previous candidates to bind and block the anti-apoptotic function of p21/waf1. After synthesizing the 24 new derivatives that are modified in their two imidazole chain, it has been successfully found that the No. 13 lead compound has the most cytotoxicity by MTT assay as well as p21 attenuating activity in ACHN and A498 cells. Moreover, the cytotoxicity of No. 13 was increased by the relatively low dose of doxorubicin treatment, a kind of conventional chemotherapies which can help to reduce the side-effect induced from the high dose use of doxorubicin treatment in patients with renal cell carcinoma.