[The selective toxic effect of dialdehyde derivatives of the pyrimidine nucleosides on human tumor cells]

Biomed Khim. 2015 Jul-Aug;61(4):497-502. doi: 10.18097/PBMC20156104497.
[Article in Russian]

Abstract

The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1-β-D-eritrofuranozyl uracil and 3'-O-β-D-ribofuranosyl-2'-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1-β-D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.

Issledovano vliianie riada sinteticheskikh proizvodnykh nukleozidov na rost i vyzhivaemost' kul'tiviruemykh kletok opukholi iaichnika cheloveka (liniia SKOV-3) i kul'tiviruemykh normal'nykh fibroblastov legkikh cheloveka. Pokazano, chto dial'degidnye proizvodnye uridina, 1--D-éritrofuranoziluratsila i 3-O--D-ribofuranozil-2-dezoksitimidina, v otlichie ot ikh neokislennykh analogov, okazyvali vyrazhennoe toksicheskoe deĭstvie na kletki SKOV-3. Kul'tiviruemye fibroblasty cheloveka okazalis' menee vospriimchivymi k povrezhdaiushchemu deĭstviiu dial'degidnykh nukleozidov. Naibol'shie razlichiia v tsitotoksicheskom deĭstvii na éti kul'tury byli vyiavleny dlia dial'degidnogo proizvodnogo 1--D-éritrofuranoziluratsila: podavlenie rosta opukholevykh kletok SKOV-3 na 50% i bolee dostigalos' pri kontsentratsiiakh étogo soedineniia v desiatki raz men'shikh, chem v sluchae normal'nykh fibroblastov.

Keywords: SKOV3 human ovarian carcinoma cell line; antitumor action; cytotoxicity; dialdehyde derivatives of nucleosides; human fibroblasts.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemical synthesis
  • Aldehydes / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytotoxins / chemical synthesis
  • Cytotoxins / pharmacology*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Furans / chemical synthesis
  • Furans / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Organ Specificity
  • Ovary / drug effects
  • Ovary / pathology
  • Uridine / analogs & derivatives
  • Uridine / chemical synthesis
  • Uridine / pharmacology*

Substances

  • Aldehydes
  • Antineoplastic Agents
  • Cytotoxins
  • Furans
  • Uridine