On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies.

Survivin protein is a metalloprotein member of the inhibitors of apoptosis proteins family, involved in the regulation of programmed cell death. Due to the recent development of antitumor therapies having survivin as molecular target, several strategies to interfere with the expression or function of survivin have emerged. This work describes the discovery of a new potential inhibitor of survivin function using a computer-aided drug design approach. Structure-based virtual screening and molecular dynamic simulations were carried out to select two compounds as possible inhibitors. According to the binding energy, possible ligand localization is in a cavity, close to dimerization interface. Next, cell-based assays were performed on three cell lines: two with tumor phenotype and over-expression of survivin, and another with normal phenotype and low expression of survivin. One of the selected compounds shows a selectively antitumor effect on panel cell lines suggesting that the compound effect could be correlated with the survivin expression.