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Antimicrobial Agents and Chemotherapy, September 2003, p. 3015-3017, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.3015-3017.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antitrypanosomal Activities of Fluoroquinolones with Pyrrolidinyl Substitutions

Elizabeth Nenortas, Tomasz Kulikowicz, Christian Burri,{dagger} and Theresa A. Shapiro*

Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore, Maryland 21205

Received 11 March 2003/ Returned for modification 16 May 2003/ Accepted 4 June 2003

Fluoroquinolones with pyrrolidinyl substitutions were tested against Trypanosoma brucei and mammalian cells. Bulky substituents at C-7 or a 1-2-bridging thiazolidine ring increased antitrypanosomal activity and selective toxicity. These compounds trap protein-DNA complexes and inhibit nucleic acid biosynthesis in trypanosomes, characteristics of topoisomerase II inhibition.

* Corresponding author. Mailing address: The Johns Hopkins University School of Medicine, 301 Hunterian Building, 725 North Wolfe St., Baltimore, MD 21205-2185. Phone: (410) 955-1888. Fax: (410) 955-2634. E-mail: tshapiro{at}jhmi.edu.

{dagger} Present address: Swiss Tropical Institute, Swiss Center for International Health, CH-4002 Basel, Switzerland.

Antimicrobial Agents and Chemotherapy, September 2003, p. 3015-3017, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.3015-3017.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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