Antileishmanial actions of tricyclic neuroleptics appear to lack structural specificity.
There is continuing interest in the antimicrobial effects of tricyclic neuroleptics and antidepressants, particularly against trypanosomatid protozoa, but few studies have attempted to dissociate antiparasitic actions from effects on the central nervous system. In this report, we have measured the antileishmanial potency of a range of structural analogues in this drug group, and conclude that no one structural determinant is critical for activity. Instead, potency may be predicted from an overall determination of the lipophilic and steric components of the structure by a simple combination of two descriptive parameters, valence connectivity and an interactive term.
Evans
A T
AT
Cell Modulation Research Unit, Faculty of Science, University of East London, U.K.
Croft
S L
SL
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000737:chemistry / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008826:Microbial Sensitivity Tests; D010640:Phenothiazines; D013329:Structure-Activity Relationship
D000929:Antidepressive Agents, Tricyclic; D000981:Antiprotozoal Agents; D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D010640:Phenothiazines; C000914:dibenzocycloheptadiene