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

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 com...

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Autores principales: Szybinski, Marcin, Brzeminski, Pawel, Fabisiak, Adrian, Berkowska, Klaudia, Marcinkowska, Ewa, Sicinski, Rafal R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666843/
https://www.ncbi.nlm.nih.gov/pubmed/29039779
http://dx.doi.org/10.3390/ijms18102162
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author Szybinski, Marcin
Brzeminski, Pawel
Fabisiak, Adrian
Berkowska, Klaudia
Marcinkowska, Ewa
Sicinski, Rafal R.
author_facet Szybinski, Marcin
Brzeminski, Pawel
Fabisiak, Adrian
Berkowska, Klaudia
Marcinkowska, Ewa
Sicinski, Rafal R.
author_sort Szybinski, Marcin
collection PubMed
description 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.
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spelling pubmed-56668432017-11-09 Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation Szybinski, Marcin Brzeminski, Pawel Fabisiak, Adrian Berkowska, Klaudia Marcinkowska, Ewa Sicinski, Rafal R. Int J Mol Sci Article 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. MDPI 2017-10-17 /pmc/articles/PMC5666843/ /pubmed/29039779 http://dx.doi.org/10.3390/ijms18102162 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szybinski, Marcin
Brzeminski, Pawel
Fabisiak, Adrian
Berkowska, Klaudia
Marcinkowska, Ewa
Sicinski, Rafal R.
Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
title Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
title_full Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
title_fullStr Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
title_full_unstemmed Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
title_short Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
title_sort seco-b-ring steroidal dienynes with aromatic d ring: design, synthesis and biological evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666843/
https://www.ncbi.nlm.nih.gov/pubmed/29039779
http://dx.doi.org/10.3390/ijms18102162
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