Rational design and synthesis of novel phenylsulfonyl-benzamides as anti-prostate cancer agents

Prostate Cancer is a major cause of male death worldwide and the identification of new efficient treatments is constantly needed. Different non-steroidal Androgen Receptor antagonists are approved also in the case of castration-resistant Cancer forms. Using a rational approach and molecular modelling studies to modify the structure of antiandrogen drug bicalutamide, a new series of phenylsulfonyl-benzamide derivatives was designed and synthesised. Their antiproliferative activities were evaluated in four different human prostate Cancer cell lines and several new compounds showed significantly improved IC₅₀ values in the low μM range. The cytotoxicity profile was also evaluated for the novel structures in the HEK293 cell line.