Issue 26, 2013

Synthesis, structural analysis and antiproliferative activity of some novel D-homo lactone androstane derivatives

Abstract

An efficient synthesis of several A,B-modified D-homo lactone androstane derivatives is reported. The synthetic scheme shows the transformation of 17-oxa-D-homoandrost-5-en-16-on-3β-yl acetate 1 into the 5α-hydroxy-17-oxa-D-homoandrostane-6,16-dion-3β-yl acetate (4). After the dehydration of 4, the newly synthesized 6-keto-androst-4-ene-3β-yl acetate derivative 5 was oximinated to give the 6-hydroximino derivative 6, which was converted to A,B-condensed isoxazole derivatives 7 and 8. Compound 4 was also converted (via 6(E)- and 6(Z)-hydroximino derivatives 9 and 10) to the B-seco-cyano derivative 11 under a Beckmann fragmentation, while compound 5 was transformed to the 4β,5β-epoxy derivative 12. Structures were confirmed by IR, 1H NMR, 13C NMR, and HRMS, and for 7 and 8 by X-ray crystallography. All compounds were tested in vitro on six malignant cell lines (MCF-7, MDA-MB-231, PC-3, HeLa, HT-29, K562) and one non-tumor MRC-5 cell line. Significant antiproliferative activity was observed for specific compounds against prostate (PC-3), cervical (HeLa) and colon (HT-29) cancer cells, while no compounds showed antiproliferative activity to non-cancerous control cells (MRC-5). Interestingly, 1–8 displayed selective antiproliferative activity against estrogen-independent (ER−, MDA-MB-231) breast cancer cells over estrogen-dependent (ER+, MCF-7) breast cancer cells.

Graphical abstract: Synthesis, structural analysis and antiproliferative activity of some novel D-homo lactone androstane derivatives

Supplementary files

Article information

Article type
Paper
Submitted
19 Mar 2013
Accepted
18 Apr 2013
First published
19 Apr 2013

RSC Adv., 2013,3, 10385-10395

Synthesis, structural analysis and antiproliferative activity of some novel D-homo lactone androstane derivatives

M. P. Savić, E. A. Djurendić, E. T. Petri, A. Ćelić, O. R. Klisurić, M. N. Sakač, D. S. Jakimov, V. V. Kojić and K. M. P. Gaši, RSC Adv., 2013, 3, 10385 DOI: 10.1039/C3RA41336E

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