17(E)-picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: antiproliferative activity and molecular docking studies.

Abstract

We report a rapid and efficient synthesis of A-ring modified 17α-picolyl and 17(E)-picolinylidene androstane derivatives from dehydroepiandrosterone. Compounds were validated spectroscopically and structurally characterized by X-ray crystallography. Virtual screening by molecular docking against clinical targets of steroidal anticancer drugs (ERα, AR, Aromatase and CYP17A1) suggests that 17(E)-picolinylidene, but not 17α-picolyl androstanes could specifically interact with CYP17A1 (17α-hydroxylase) with similar geometry and affinity as Abiraterone, a 17-pyridinyl androstane drug clinically used in the treatment of prostate cancer. In addition, several 17(E)-picolinylidene androstanes demonstrated selective antiproliferative activity against PC3 prostate cancer cells, which correlates with Abiraterone antiproliferative activity and predicted CYP17A1 binding affinities. Based on these preliminary results, 17(E)-picolinylidene androstane derivatives could be a promising starting point for the development of new compounds for the treatment of prostate cancer.

DOI: 10.1016/j.bmc.2013.09.063

Cite this paper

@article{Ajdukovi201317EpicolinylideneAD, title={17(E)-picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: antiproliferative activity and molecular docking studies.}, author={Jovana J Ajdukovi{\'c} and Evgenija A. Djurendi{\'c} and Edward Petri and Olivera R. Klisuri{\'c} and Andjelka S {\'C}eli{\'c} and Marija N. Saka{\vc} and Dimitar S. Jakimov and Katarina M Penov Ga{\vs}i}, journal={Bioorganic & medicinal chemistry}, year={2013}, volume={21 23}, pages={7257-66} }