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

  • Bioorg Med Chem. 2013 Dec 1;21(23):7257-66. doi: 10.1016/j.bmc.2013.09.063.
Jovana J Ajduković  1 ,  Evgenija A Djurendić ,  Edward T Petri ,  Olivera R Klisurić ,  Andjelka S Celić ,  Marija N Sakač ,  Dimitar S Jakimov ,  Katarina M Penov Gaši
Affiliations
  • 1. Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: [email protected].
PMID: 24148837 DOI: 10.1016/j.bmc.2013.09.063
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.

Keywords
17α-Picolyl and 17(E)-picolinylidene derivatives; Androstane; Antiproliferative activity; Antitumor; MWVNCXYRJNBSNB-ROWBJTNXSA-N; Molecular docking; Synthesis; Virtual screening.