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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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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. |
format | Online Article Text |
id | pubmed-5666843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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