2. Academic Validation
  3. Synthesis, structural analysis and antitumor activity of novel 17α-picolyl and 17(E)-picolinylidene A-modified androstane derivatives

Synthesis, structural analysis and antitumor activity of novel 17α-picolyl and 17(E)-picolinylidene A-modified androstane derivatives

  • Bioorg Med Chem. 2015 Apr 1;23(7):1557-68. doi: 10.1016/j.bmc.2015.02.001.
Jovana J Ajduković 1,  Katarina M Penov Gaši 2,  Dimitar S Jakimov 3,  Olivera R Klisurić 4,  Suzana S Jovanović-Šanta 2,  Marija N Sakač 2,  Lidija D Aleksić 3,  Evgenija A Djurendić 2
Affiliations

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: jovana.ajdukovic@dh.uns.ac.rs.
  • 2 Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
  • 3 Oncology Institute of Vojvodina, Put Dr. Goldmana 4, 21204 Novi Sad, Serbia.
  • 4 Department of Physics, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 4, 21000 Novi Sad, Serbia.
PMID: 25737400 DOI: 10.1016/j.bmc.2015.02.001
Abstract

The heterocyclic ring at C-17 position of the androstane compounds plays an important role in biological activity. The aim of the present study was to synthesize and evaluate potential antitumor activity of different A-modified 17α-picolyl and 17(E)-picolinylidene androstane derivatives. In several synthetic steps, novel derivatives bearing the hydroximino, nitrile or lactame functions in A-ring were synthesized and characterized according to the spectral data, by mass analysis as well as XRD analysis (compounds 6, 13 and 15). The structurally most promising compounds 6, 11-17 were investigated as antitumor agents. The in vitro antiproliferative activity was evaluated against six human Cancer cell lines: Estrogen Receptor negative (ER-) breast adenocarcinoma (MDA-MB-231); Estrogen Receptor positive (ER+) breast adenocarcinoma (MCF-7); prostate Cancer (PC-3); human cervical carcinoma (HeLa); lung adenocarcinoma (A549) and colon adenocarcinoma (HT-29) using MTT assay. The results of the 48h incubation time in vitro tests showed that compound 15 was the most effective against PC-3 (IC50 6.6μM), compound 17 against MCF-7 (IC50 7.9μM) cells, while compound 16 exhibited strong antiproliferative effect against both, MCF-7 (IC50 1.7μM) and PC-3 (IC50 8.7μM) Cancer cells. It was also found that compounds 16 and 17 induced Apoptosis in MCF-7 cells (dicyano derivative 17 stronger then dioxime 16 and reference formestane), with no distinct changes in the cell cycle of MCF-7 cells.

Keywords

Androstane derivatives; Antiproliferative activity; Apoptosis; Synthesis; X-ray.

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