Emma C. Rivers and Ricardo L. Mancera Pages 1956 - 1967 ( 12 )
It is estimated that a third of the worlds population is currently infected with tuberculosis, leading to 1.6 million deaths annually. The current drug regimen is 40 years old and takes 6-9 months to administer. In addition, the emergence of drug resistant strains and HIV co-infection mean that there is an urgent need for new anti-tuberculosis drugs. The twenty-first century has seen a revival in research and development activity in this area, with several new drug candidates entering clinical trials. This review considers new potential firstline anti-tuberculosis drug candidates, in particular those with novel mechanisms of action, as these are most likely to prove effective against resistant strains. A brief overview of current first-line and recent drugs (such as fluoroquinolones, rifampicin and isoniazid analogues) is initially presented. This is followed by a description of structure-activity relationships, in vitro and in vivo activity, pharmacokinetics, mechanism of action, combination regimens and clinical trials of the new drug candidates SQ109, PA-824, OPC-67683, TMC207 and others.
Mycobacterium tuberculosis,drug action,SQ109,PA-824,OPC-67683,TMC207/R207910
, Western Australian Biomedical Research Institute, School of Pharmacy and School of Biomedical Sciences, Curtin University of Technology, GPO Box U1987, Perth WA 6845, Australia.