Immunoregulatory effects of N9-benzyl- and N7-benzyl-8-bromoguanines

L. Poluektova, M. Madre, R. Zhuk, N. Osna, L. Somashenkova, A. Zvirbliene, A. Socnev, M. M. Khan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In this study we investigated the effects of two guanine derivatives, 9-benzyl- (I) and 7-benzyl-8-bromoguanines (II) on the proliferation of human T-cell leukemia and T-cell lymphoma, normal human peripheral blood mononuclear cells (PBMC), and mouse Th1 (pGL10) and Th2 (D10.G4.1) clones. We also assessed their effects on cytokine production (IL-3, IL-10 and IFN-γ) in PBMC, T-cell lymphoma, HUT78 (IL-2), and murine Th1 (IL-2) and Th2 (IL-4 and IL-5) clones. These compounds were synthesize as analog of known inhibitors of purine nucleoside phosphorylase (PNP) 8-amino-9-benzyl-guanine. These compounds suppressed proliferation of human leukemia MOLT-4 cells, human cutaneous lymphoma HUT78 cells and normal PMBC. Compound II was a significantly more potent inhibitor than compound I. Exogenous recombinant human IL-2 reversed the anti-proliferative effects of both compounds on HUT78 cells. These compounds had low toxicity to human EBV-transformed B-lymphocytes. Both compounds suppressed the production of IL-2 by activated human HUT78 cells, IFN-γ by PBMC and did not affect IL-3 and IL-10 production in PBMC. Compound I inhibited anti-CD3-activated IL-2 secretion from the murine Th1 clone. The murine Th2 clone was less sensitive to both compounds as compared with Th1. The production of IL-4 and IL-5 by this clone was not suppressed. Thus, it has been shown that not only 9-substituted guanines but also their 7-isomers selectively inhibit T-cell functions and both selectively inhibit Th1-related cytokines secretion. Copyright (C) 1999 International Society for Immunopharmacology.

Original languageEnglish (US)
Pages (from-to)777-792
Number of pages16
JournalInternational Journal of Immunopharmacology
Volume21
Issue number11
DOIs
StatePublished - Nov 1999

Keywords

  • -4
  • -5
  • 7-benzyl-8-bromoguanine
  • 9-benzyl-8-bromoguanine
  • Cell proliferation
  • Interferon-γ
  • Interleukin-2

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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