Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
AbstractContinuing 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
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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.
Szybinski M, Brzeminski P, Fabisiak A, Berkowska K, Marcinkowska E, Sicinski RR. Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation. International Journal of Molecular Sciences. 2017; 18(10):2162.Chicago/Turabian Style
Szybinski, Marcin; Brzeminski, Pawel; Fabisiak, Adrian; Berkowska, Klaudia; Marcinkowska, Ewa; Sicinski, Rafal R. 2017. "Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation." Int. J. Mol. Sci. 18, no. 10: 2162.
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