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.
|Number of pages||6|
|Issue number||6 B|
|Publication status||Published - Dec 1 1992|
- Biological activity of plasmid DNA
- Cannabidiolic acid plasmid elimination
ASJC Scopus subject areas
- Cancer Research