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Antimicrobial Agents and Chemotherapy, October 2003, p. 3368-3370, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3368-3370.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Activity of Megazol, a Trypanocidal Nitroimidazole, Is Associated with DNA Damage

Bertin Enanga,1 Mark R. Ariyanayagam,2 Mhairi L. Stewart,1 and Michael P. Barrett1*

Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ,1 Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom2

Received 1 May 2003/ Returned for modification 19 June 2003/ Accepted 18 July 2003

DNA damage associated with the trypanocidal activity of megazol [2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole] was shown in experiments in which DNA repair-deficient RAD51-/- Trypanosoma brucei mutants were found to be hypersensitive to the drug. Parasites resistant to megazol were selected and showed modest cross-resistance to other trypanocides, although neither drug efflux nor changes to intracellular thiols correlated with resistance.

* Corresponding author. Mailing address: University of Glasgow, Institute of Biomedical and Life Sciences, Division of Infection and Immunity, The Joseph Black Building, Glasgow G12 8QQ, United Kingdom. Phone and fax: 44-141-330-6904. E-mail: m.barrett{at}bio.gla.ac.uk.

Antimicrobial Agents and Chemotherapy, October 2003, p. 3368-3370, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3368-3370.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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