INHIBITION OF BACTERIAL PLASMID REPLICATION BY STEREOSELECTIVE BINDING BY TRICYCLIC PSYCHOPHARMACONS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 43  (2) , 235-249
Abstract
Several dibenzoazepines, thioxanthene and phenothiazine stereoisomers were studied for their abilities to inhibit plasmid replication, intracellular transfer of R-plasmid, bacterial ATPase and mouse serum cholinesterase isoenzymes. A partially saturated derivative of desipramine inhibited plasmid replication and transfer; the fully saturated derivative was inactive. The inhibition of plasmid curing and transfer patterns did not correlate with the inhibition of ATPase and cholinesterase. Trans-clopenthixol was more effective in plasmid elimination than the cis isomer. The cis isomer inhibited ATPase and cholinesterase more than the trans isomer; (-)- and (+)-methoxytrimeprazine also inhibited plasmid replication and enzyme activity. The tricyclic configuration of the drugs tested for stereospecific binding to bacterial receptors may be more important than its side chain orientation. There may be a similarity between bacterial receptor sites and neural receptor sites. Therefore, this model may be useful in the study of neuropharmacological agents as potential antibacterial agents.