Mechanism of action of tricyclic drugs on Esherichia coli and Yersinia enterocolitica plasmid maintenance and replication

K. Csiszar, J. Molnar

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18 Citations (Scopus)

Abstract

Tricyclic medical compounds like many other nonantibiotics exhibit antimicrobial activities. Two chemically representative groups were tested in plasmid DNA transformation and replication to assign intracellular target sites responsible for the multiple effects in Esherichia coli and Yersinia enterocolitica cells. To analyse the mechanism of action at the molecular level, the effects of chlorpromazine, 7,8 dioxochlorpromazine, promethazine, methylene blue, imipramine, cannabidiolic acid and tetrahydrocannabidiolic acid were examined at several points in the course of transformation, in plasmid replication and on the topologycal state of plasmid DNA. Two possible target sites were identified, one of them involving membrane binding sites which participate in plasmid DNA replication. Drug binding at these sites interfered with the replicating plasmid DNA and membrane protein complex, preventing the proper processing of the replication that resulted in plasmid loss. The other in vivo and in vitro effect was observed on the topological state of plasmid DNA. Tricyclic drugs interfered with energy dependent gyrase activity and promoted the relaxation of plasmid DNA, causing disturbances in gene expression and in plasmid replication. The results give insight into the chemical structures connected with significant specific antimicrobial effects.

Original languageEnglish
Pages (from-to)2267-2272
Number of pages6
JournalAnticancer research
Volume12
Issue number6 B
Publication statusPublished - Dec 1 1992

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Keywords

  • Biological activity of plasmid DNA
  • Cannabidiolic acid plasmid elimination
  • Dibenzoazepines
  • Phenothiazines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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