Design, synthesis and biological evaluation of novel 2-alkylidene 19-norcalcitriol analogs

0531937 - ÚEB 2021 RIV US eng J - Journal Article
Fabisiak, A. - Brzeminski, P. - Berkowska, K. - Rárová, Lucie - Marcinkowska, A. - Sicinski, R. R.
Design, synthesis and biological evaluation of novel 2-alkylidene 19-norcalcitriol analogs.
Bioorganic Chemistry. Roč. 101, AUG (2020), č. článku 104013. ISSN 0045-2068. E-ISSN 1090-2120
R&D Projects: GA ČR(CZ) GA19-01383S
Institutional support: RVO:61389030
Keywords : 19-Norcalcitriol * Drug delivery systems * Platinum(II) complexes * Vitamin D receptor * Wittig-Horner reaction
OECD category: Organic chemistry
Impact factor: 5.275, year: 2020
Method of publishing: Open access
http://doi.org/10.1016/j.bioorg.2020.104013

Continuing our studies aimed at A-ring modified vitamin D compounds, we designed novel 19-norcalcitriol derivatives bearing at C-2 pegylated chains of different lengths. The terminal fragments of these substituents contain hydroxyls or moieties possessing nitrogen and/or sulfur atoms capable of transition metal ions complexation. Also, two conjugate–type platinum(II) complexes of 19-norcalcitriol were obtained in which L-methionine served as chelating moiety. The convergent synthesis of the target 19-norcalcitriol analogs involved several steps with the crucial one being condensation of A-ring phosphine oxide and the known Grundmann ketone by Wittig-Horner reaction. Further elaboration of the 2-alkylidene substituent provided all final compounds which were then tested to determine their affinity for the vitamin D receptor and cytotoxic activity.
Permanent Link: http://hdl.handle.net/11104/0310568