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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F20%3A00531676" target="_blank" >RIV/61389030:_____/20:00531676 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/20:73604439

Result on the web

<a href="http://doi.org/10.1016/j.bioorg.2020.103883" target="_blank" >http://doi.org/10.1016/j.bioorg.2020.103883</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2020.103883" target="_blank" >10.1016/j.bioorg.2020.103883</a>

Result language

angličtina

Original language name

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

Original language description

Hormonally 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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10401 - Organic chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

—

Volume of the periodical

100

Issue of the periodical within the volume

JUL

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

103883

UT code for WoS article

000540958600011

EID of the result in the Scopus database

2-s2.0-85083883029