Biological activity of N(4)-boronated derivatives of 2'-deoxycytidine, potential agents for boron-neutron capture therapy.
Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system.
Rzeszów University of Technology, Faculty of Chemistry, Bioorganic Chemistry Laboratory, 6 Powstańców Warszawy Ave., 35-959 Rzeszów, Poland.
Joanna
J
Nizioł
Rzeszów University of Technology, Faculty of Chemistry, Bioorganic Chemistry Laboratory, 6 Powstańców Warszawy Ave., 35-959 Rzeszów, Poland.
Łukasz
Ł
Uram
Rzeszów University of Technology, Faculty of Chemistry, Bioorganic Chemistry Laboratory, 6 Powstańców Warszawy Ave., 35-959 Rzeszów, Poland.
Magdalena
M
Szuster
Rzeszów University of Technology, Faculty of Chemistry, Bioorganic Chemistry Laboratory, 6 Powstańców Warszawy Ave., 35-959 Rzeszów, Poland.
Justyna
J
Sekuła
Rzeszów University of Technology, Faculty of Chemistry, Bioorganic Chemistry Laboratory, 6 Powstańców Warszawy Ave., 35-959 Rzeszów, Poland. Electronic address: tomruman@prz.edu.pl.
Tomasz
T
Ruman
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001895:Boron / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis / Q000302:isolation & purification; D003841:Deoxycytidine / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D003841:Deoxycytidine; D001895:Boron
Boron nucleoside; Boron nucleotide; Boron-neutron capture therapy; DNA fragmentation; DNA mass spectrometry