2',3'-Dideoxyuridine triphosphate conjugated to SiO2 nanoparticles: Synthesis and evaluation of antiproliferative activity

Svetlana V Vasilyeva; Inga R Grin; Boris P Chelobanov; Dmitry A Stetsenko

doi:10.1016/j.bmcl.2018.02.007

2',3'-Dideoxyuridine triphosphate conjugated to SiO₂ nanoparticles: Synthesis and evaluation of antiproliferative activity

Bioorg Med Chem Lett. 2018 Apr 15;28(7):1248-1251. doi: 10.1016/j.bmcl.2018.02.007. Epub 2018 Feb 7.

Authors

Svetlana V Vasilyeva¹, Inga R Grin², Boris P Chelobanov², Dmitry A Stetsenko³

Affiliations

¹ Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia. Electronic address: svetlana2001@gmail.com.
² Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia; Novosibirsk State University, Novosibirsk 630090, Russia.
³ Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia.

PMID: 29506959
DOI: 10.1016/j.bmcl.2018.02.007

Abstract

A conjugate of triphosphorylated 2',3'-dideoxyuridine (ddU) with SiO₂ nanoparticles was obtained via the CuAAC click chemistry between a γ-alkynyl ddU triphosphate and azido-modified SiO₂ nanoparticles. Assessment of cytotoxicity in human breast adenocarcinoma MCF7 cells demonstrated that ddU triphosphate conjugated to SiO₂ nanoparticles exhibited a 50% decrease in cancer cell growth at a concentration of 183 ± 57 µg/mL, which corresponds to 22 ± 7 µM of the parent nucleotide, whereas the parent nucleoside, nucleotide and alkynyl triphosphate precursor do not show any cytotoxicity. The data provide an example of remarkable potential of novel conjugates of SiO₂ nanoparticles with phosphorylated nucleoside analogues, even those, which have not been used previously as therapeutics, for application as new anticancer agents.

Keywords: 2′, 3′-Dideoxyuridine triphosphate; CuAAC; Cytotoxicity; MCF7 cells; SiO(2) nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Dideoxynucleotides / chemical synthesis
Dideoxynucleotides / chemistry
Dideoxynucleotides / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
MCF-7 Cells
Molecular Structure
Nanoparticles / chemistry*
Silicon Dioxide / chemistry
Silicon Dioxide / pharmacology*
Structure-Activity Relationship
Uracil Nucleotides / chemical synthesis
Uracil Nucleotides / chemistry
Uracil Nucleotides / pharmacology*

Substances

Antineoplastic Agents
Dideoxynucleotides
Uracil Nucleotides
Silicon Dioxide
2',3'-dideoxyuridine-5'-triphosphate