Studies on the effect of CL 306,293, a substituted quinoline carboxylic acid, on the clinical disease induced in mice with LP-BM5 virus

Antiviral Res. 1993 Jan;20(1):71-81. doi: 10.1016/0166-3542(93)90060-v.

Abstract

CL 306,293, a substituted quinoline carboxylic acid, is a potent inhibitor of dihydroorotic acid dehydrogenase, an enzyme essential for the biosynthesis of pyrimidines. In mammalian cell culture, the agent exhibits antiproliferative properties that can be reversed by the addition of uridine. CL 306,293 inhibits the development of the clinical disease in a murine model of immunodeficiency induced by a mixture of LP-BM5 retroviruses. In infected mice, the agent prevents the development of hypergammaglobulinemia, lymphadenopathy, splenomegaly and induction of an IL-2 deficiency. The CD4/CD8 ratio and the number of B cells in the lymph nodes are decreased if the infected animals are treated with CL 306,293. CL 306,293 was more efficacious and potent than 3'-azido-3'-deoxythymidine. The beneficial effects of CL 306,293 observed in this model are most probably related to its antiproliferative properties.

Publication types

  • Comparative Study

MeSH terms

  • AIDS-Related Complex
  • Aminoquinolines / therapeutic use*
  • Aminoquinolines / toxicity
  • Animals
  • Antibodies, Viral / blood
  • B-Lymphocytes / physiology
  • Biphenyl Compounds / therapeutic use*
  • Biphenyl Compounds / toxicity
  • CD4-CD8 Ratio
  • Cells, Cultured
  • Dihydroorotate Oxidase / antagonists & inhibitors*
  • Fibroblasts / drug effects
  • Hypergammaglobulinemia
  • Immunoglobulin M / analysis
  • Interleukin-2 / deficiency
  • Mice
  • Mice, Inbred C57BL
  • Murine Acquired Immunodeficiency Syndrome / drug therapy*
  • Murine Acquired Immunodeficiency Syndrome / enzymology
  • Recurrence
  • Splenomegaly
  • Zidovudine / therapeutic use

Substances

  • Aminoquinolines
  • Antibodies, Viral
  • Biphenyl Compounds
  • Immunoglobulin M
  • Interleukin-2
  • 3-amino-2-(1,1'-biphenyl)-4-yl-6-fluoro-4-quinolinecarboxylic acid
  • Zidovudine
  • Dihydroorotate Oxidase