Conjugates of phosphorylated zalcitabine and lamivudine with SiO 2 nanoparticles: Synthesis by CuAAC click chemistry and preliminary assessment of anti-HIV and antiproliferative activity.

Autor: Vasilyeva SV; 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., Shtil AA; N. N. Blokhin Cancer Center, Moscow, Russia., Petrova AS; N. N. Blokhin Cancer Center, Moscow, Russia., Balakhnin SM; Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia., Achigecheva PY; State Research Centre of Virology and Biotechnology 'Vector', Koltsovo, Russia., Stetsenko DA; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia., Silnikov VN; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2017 Mar 01; Vol. 25 (5), pp. 1696-1702. Date of Electronic Publication: 2017 Jan 25.
DOI: 10.1016/j.bmc.2017.01.038
Abstrakt: Conjugates of phosphorylated dideoxynucleoside antiviral drugs dideoxycytidine (zalcitabine) and lamivudine with SiO 2 nanoparticles were obtained via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry between a nucleoside triphosphate containing an alkynyl group at the γ-phosphate or azidothymidine triphosphate and SiO 2 nanoparticles containing alkyl azide or alkynyl groups, respectively. 4-(Prop-2-yn-1-yloxy)butylamino group has been attached to the γ-phosphate group of dideoxycytidine (zalcitabine) and lamivudine 5'-triphosphates via the phosphoramidate linkage. New compounds were shown to be potent killers of human colon carcinoma cells. Anti-HIV activity of the conjugates was demonstrated as well. The conjugates of phosphorylated lamivudine and dideoxycytidine (zalcitabine) showed higher potency than the parent nucleosides. The conjugate of phosphorylated azidothymidine was less active against HIV-1 than the parent nucleoside probably because of the replacement of its 3'-azido group by 1,2,3-triazole ring. These results show an opportunity for using SiO 2 nanoparticles as a transport for delivering phosphorylated nucleosides to cells in order to increase their efficiency as antiviral and anticancer drugs.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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