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Synthesis of Gemini analogs of 19-norcalcitriol and their platinum(II) complexes.

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cris.lastimport.scopus2024-02-12T19:44:01Z
dc.abstract.enHormonally active vitamin D3 metabolite, calcitriol, plays an important role in calcium-phosphate homeostasis, immune system actions and cell differentiation. Although anticancer activity of calcitriol is well documented and thousands of its analogs have been synthesized, none has been approved as a potential drug against cancer. Therefore, we attempted to introduce the cytotoxic effect to the calcitriol molecule by its linking to cisplatin. Herein, we present the synthesis of vitamin D compounds, designed on the basis of molecular modeling and docking experiments to the vitamin D receptor, and characterized by the presence of significantly different two side chains attached to C-20. In this study, a new synthetic approach to Gemini analogs was developed. Preparation of the target 19-norcalcitriol compounds involved separate syntheses of several building blocks (the A-ring, C/D-rings and side-chain fragments). The convergent synthetic strategy was used to combine these components by the different coupling processes, the crucial one being Wittig-Horner reaction of the Grundmann ketone analog with the known 2-methylene A-ring phosphine oxide. Due to the nature of the constructed steroidal side chains (bidentate ligands), which allowed coordination of metal ions, the first conjugate-type platinum(II) complexes of the vitamin D analogs were also successfully prepared and characterized. The target vitamin D compounds, displaying significant affinity for a vitamin D receptor, were assessed in vitro for their anti-proliferative activities towards several cell lines.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorRárová, Lucie
dc.contributor.authorMarcinkowska, Ewa
dc.contributor.authorSiciński, Rafał
dc.contributor.authorFabisiak, Adrian
dc.contributor.authorBerkowska, Klaudia
dc.contributor.authorBrzemiński, Paweł
dc.date.accessioned2024-01-26T09:26:48Z
dc.date.available2024-01-26T09:26:48Z
dc.date.issued2020
dc.description.financePublikacja bezkosztowa
dc.description.volume100
dc.identifier.doi10.1016/J.BIOORG.2020.103883
dc.identifier.issn0045-2068
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/121308
dc.identifier.weblinkhttp://doi.org/10.1016/j.bioorg.2020.103883
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofBioorganic Chemistry
dc.relation.pages103883
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.en19-Norcalcitriol
dc.subject.enGemini compounds
dc.subject.enVitamin D receptor
dc.subject.enWittig-Horner reaction
dc.subject.enPlatinum(II) complexes
dc.subject.enDrug delivery systems
dc.titleSynthesis of Gemini analogs of 19-norcalcitriol and their platinum(II) complexes.
dc.typeJournalArticle
dspace.entity.typePublication