title: 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.
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: Jovana.Ajdukovic@dh.uns.ac.rs.
authors.forename: Jovana J
authors.initials: JJ
authors.lastname: Ajduković
authors.forename: Evgenija A
authors.initials: EA
authors.lastname: Djurendić
authors.forename: Edward T
authors.initials: ET
authors.lastname: Petri
authors.forename: Olivera R
authors.initials: OR
authors.lastname: Klisurić
authors.forename: Andjelka S
authors.initials: AS
authors.lastname: Celić
authors.forename: Marija N
authors.initials: MN
authors.lastname: Sakač
authors.forename: Dimitar S
authors.initials: DS
authors.lastname: Jakimov
authors.forename: Katarina M Penov
authors.initials: KM
authors.lastname: Gaši
mesh_terms: D000731:Androstanes / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D011467:Prostate / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011485:Protein Binding; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000731:Androstanes; D000970:Antineoplastic Agents; D013254:Steroid 17-alpha-Hydroxylase; C033936:androstane
keywords: 17α-Picolyl and 17(E)-picolinylidene derivatives; Androstane; Antiproliferative activity; Antitumor; MWVNCXYRJNBSNB-ROWBJTNXSA-N; Molecular docking; Synthesis; Virtual screening