Synthesis of halogen-substituted 3-deazaadenosine and 3-deazaguanosine analogues as potential antitumor/antiviral agents

Nucleosides Nucleotides Nucleic Acids. 2001 Dec;20(12):1975-2000. doi: 10.1081/NCN-100108327.

Abstract

Various 2-halogen-substituted analogues (38, 39, 43 and 44), 3-halogen-substituted analogues (51 and 52), and 2',3'-dihalogen-substituted analogues (57-60) of 3-deazaadenosine and 3-halogen-substituted analogues (61 and 62) of 3-deazaguanosine have been synthesized as potential anticancer and/or antiviral agents. Among these compounds, 3-deaza-3-bromoguanosine (62) showed significant cytotoxicity against L1210, P388, CCRF-CEM and B16F10 cell lines in vitro, producing IC50 values of 3, 7, 9 and 7 microM, respectively. Several 3-deazaadenosine analogues (38, 51, 57 and 59) showed moderate to weak activity against hepatitis B virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Biochemistry / methods
  • Drug Screening Assays, Antitumor
  • Guanosine / analogs & derivatives*
  • Guanosine / chemical synthesis*
  • Guanosine / chemistry
  • Guanosine / pharmacology*
  • HIV-1 / drug effects
  • Halogens / chemistry
  • Hepatitis B virus / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Leukemia L1210
  • Microbial Sensitivity Tests
  • Tumor Cells, Cultured

Substances

  • 3-deaza-3-bromoguanosine
  • Antineoplastic Agents
  • Antiviral Agents
  • Halogens
  • Guanosine
  • 3-deazaguanosine