Cargando…

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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.