Open Access

The immunosuppressive activities of newly synthesized azaphenothiazines in human and mouse models

  • Michał Zimecki1,
  • Jolanta Artym1,
  • Maja Kocięba1,
  • Krystian Pluta2Email author,
  • Beata Morak-Młodawska2 and
  • Małgorzata Jeleń2
Cellular & Molecular Biology LettersAn International Journal200914:25

https://doi.org/10.2478/s11658-009-0025-1

Received: 11 December 2008

Accepted: 9 June 2009

Published: 25 June 2009

Abstract

In this study, we evaluated the activities of new types of azaphenothiazines in the following immunological assays: the proliferative response of human peripheral blood mononuclear cells induced by phytohemagglutin A or anti-CD3 antibodies; lipopolysaccharide-induced cytokine production by human PBMC; the secondary, humoral immune response in mice to sheep erythrocytes (in vitro); and delayed-type hypersensitivity in mice to ovalbumin (in vivo). In some tests, chlorpromazine served as a reference drug. The compounds exhibited differential inhibitory activities in the proliferation tests, with 10H-2,7-diazaphenothiazine (compound 1) and 6-(3-dimethylaminopropyl)diquinothiazine (compound 8) being most suppressive. Compound 1 was selected for further studies, and was found to be strongly suppressive in the humoral immune response even at low concentrations (1 μg/ml). Compound 1 also inhibited the delayed-type hypersensitivity lipopolysaccharide-induced production of tumor necrosis factor and interleukin-6 in cultures of human blood cells. As there were only two subjects in this study, the effects of these compounds on human blood cells need to be confirmed. In this paper, we also discuss the structure-activity relationships of selected compounds.

Key words

AzaphenothiazinesImmune responsePBMCProliferationCytokines

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