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Int. J. Mol. Sci. 2017, 18(10), 2162; https://doi.org/10.3390/ijms18102162

Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation

1
Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
2
Department of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland
*
Author to whom correspondence should be addressed.
Received: 28 September 2017 / Revised: 13 October 2017 / Accepted: 14 October 2017 / Published: 17 October 2017
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Abstract

Continuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds could mimic the ligands with a good affinity to the vitamin D receptor (VDR). Multi-step synthesis of the C/D-ring building block of the tetralone structure was achieved and its enol triflate was coupled with the known A-ring fragments, possessing conjugated enyne moiety, using Sonogashira protocol. The structures of the final products were confirmed by NMR, UV and mass spectroscopy. Their binding affinities for the full-length human VDR were determined and it was established that compound substituted at C-2 with exomethylene group showed significant binding to the receptor. This analog was also able to induce monocytic differentiation of HL-60 cells. View Full-Text
Keywords: steroidal dienynes; B-seco steroids; Sonogashira reaction; vitamin D receptor; HL-60 cell differentiation steroidal dienynes; B-seco steroids; Sonogashira reaction; vitamin D receptor; HL-60 cell differentiation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Szybinski, M.; Brzeminski, P.; Fabisiak, A.; Berkowska, K.; Marcinkowska, E.; Sicinski, R.R. Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation. Int. J. Mol. Sci. 2017, 18, 2162.

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