Inhibition of bacterial plasmid replication by stereoselective binding by tricyclic psychopharmacons.
Several dibenzazepines, thioxanthene, and phenothiazine stereoisomers were studied for their abilities to inhibit plasmid replication, intracellular transfer of R-plasmid, bacterial ATP-ase, and mouse serum cholinesterase isoenzyme. Partially saturated derivative of desipramine inhibited plasmid replication and transfer, but the fully saturated derivative was inactive. The inhibition of plasmid curing and transfer patterns did not correlate with the inhibition of ATP-ase and cholinesterase. Trans-clopenthixol was more effective in plasmid elimination than the cis-isomer. On the other hand, the cis-isomer inhibited ATP-ase and cholinesterase more than the trans-isomer. The levo- and dextro-methoxytrimeprazine also inhibited plasmid replication and enzyme activity. We believe that the tricyclic configuration of the drugs tested for stereospecific binding to bacterial receptors is more important than its side chain orientation. We believe that there is 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.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003227:Conjugation, Genetic / Q000187:drug effects*; D003470:Culture Media; D003891:Desipramine / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008728:Methotrimeprazine / Q000494:pharmacology; D010957:Plasmids / Q000187:drug effects*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011815:R Factors / Q000187:drug effects*; D013237:Stereoisomerism
D000929:Antidepressive Agents, Tricyclic; D003470:Culture Media; D011619:Psychotropic Drugs; D000255:Adenosine Triphosphate; D008728:Methotrimeprazine; D003891:Desipramine