Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT

Rachel L Clark; Carol J Clements; Michael P Barrett; Simon P Mackay; Rajendra P Rathnam; George Owusu-Dapaah; John Spencer; Judith K Huggan

doi:10.1016/j.bmc.2012.08.049

Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT

Bioorg Med Chem. 2012 Oct 15;20(20):6019-33. doi: 10.1016/j.bmc.2012.08.049. Epub 2012 Aug 31.

Authors

Rachel L Clark¹, Carol J Clements, Michael P Barrett, Simon P Mackay, Rajendra P Rathnam, George Owusu-Dapaah, John Spencer, Judith K Huggan

Affiliation

¹ Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.

PMID: 22985960
DOI: 10.1016/j.bmc.2012.08.049

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzodiazepines / chemistry*
Benzodiazepines / pharmacology
Benzodiazepines / therapeutic use
Humans
Microbial Sensitivity Tests
Quinazolines / chemistry*
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 therapy

Substances

Quinazolines
Trypanocidal Agents
Benzodiazepines