ABSTRACT
A library of 1,4-benzodiazepines has been synthesised and evaluated for activity against Trypanosoma brucei, a causative parasite of Human African Trypanosomiasis (HAT). The most potent of these derivatives has an MIC value of 0.97 µM. Herein we report the design, synthesis and biological evaluation of the abovementioned compounds.
Subject(s)
Benzodiazepines/chemistry , Quinazolines/chemistry , Animals , Benzodiazepines/pharmacology , Benzodiazepines/therapeutic use , Humans , Microbial Sensitivity Tests , Quinazolines/pharmacology , Quinazolines/therapeutic use , Structure-Activity Relationship , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/pharmacology , Trypanocidal Agents/therapeutic use , Trypanosoma brucei brucei/drug effects , Trypanosomiasis, African/drug therapyABSTRACT
The continual increase in drug resistance; the lack of new chemotherapeutic agents; the toxicity of existing agents and the increasing morbidity with HIV co-infection mean the search for new antileishmanial agents has never been more urgent. We have identified the benzodiazepines as a structural class for antileishmanial hit optimisation, and demonstrated that their in vitro activity is comparable with the clinically used drug, sodium stibogluconate, and that the compounds are not toxic to macrophages.
