Conjugates of phosphorylated zalcitabine and lamivudine with SiO2nanoparticles: Synthesis by CuAAC click chemistry and preliminary assessment of anti-HIV and antiproliferative activity.
Conjugates of phosphorylated dideoxynucleoside antiviral drugs dideoxycytidine (zalcitabine) and lamivudine with SiO2nanoparticles 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 SiO2nanoparticles 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 SiO2nanoparticles as a transport for delivering phosphorylated nucleosides to cells in order to increase their efficiency as antiviral and anticancer drugs.
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.
Svetlana V
SV
Vasilyeva
N. N. Blokhin Cancer Center, Moscow, Russia.
Alexander A
AA
Shtil
N. N. Blokhin Cancer Center, Moscow, Russia.
Albina S
AS
Petrova
Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia.
Sergei M
SM
Balakhnin
State Research Centre of Virology and Biotechnology "Vector", Koltsovo, Russia.
Polina Y
PY
Achigecheva
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia.
Dmitry A
DA
Stetsenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia.
Vladimir N
VN
Silnikov
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D057930:Click Chemistry; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D010766:Phosphorylation; D012822:Silicon Dioxide / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D016047:Zalcitabine / Q000737:chemistry* / Q000494:pharmacology
D019380:Anti-HIV Agents; D019259:Lamivudine; D016047:Zalcitabine; D012822:Silicon Dioxide
Colon cancer cells; Copper(I)-catalyzed azide-alkyne cycloaddition; Cytotoxicity; HIV-1; Phosphorylated dideoxynucleoside analogues; SiO(2) nanoparticles