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Repurposing amiloride derivatives as new agents for drug-resistant tuberculosis

Year:
2016
Duration:
41 months
Approved budget:
$1,186,404.55
Researchers:
Professor Gregory Cook
Health issue:
Infectious disease
Proposal type:
Project
Lay summary
Tuberculosis (TB) disease is increasing and drug-resistant M. tuberculosis strains are becoming more prevalent through the importation of these strains from high incidence countries (Asia-Pacific). Treatment options for drug-resistant strains are limited and expensive, creating an urgent need to develop new TB drugs. New drugs to combat TB disease should be centred on inhibitors of energy generation as these agents have the greatest potential to shorten TB chemotherapy to 8 weeks (e.g. bedaquiline). The goal of our study is to perform a structure-activity exploration of amiloride analogues against M. tuberculosis to identify potent new inhibitors of tuberculosis disease to combat drug resistance. The development of fast-acting drugs that combat all forms of TB disease will result in a reduction of the incidence of TB in New Zealand amongst those at greatest risk (e.g. Maori and Pacific Island descent) and individuals living in socioeconomically deprived areas (55% of all TB cases).