title: Antitrypanosomal activities of fluoroquinolones with pyrrolidinyl substitutions.
abstract: 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.
authors.affiliation: Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nenortas
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kulikowicz
authors.forename: Christian
authors.initials: C
authors.lastname: Burri
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D024841:Fluoroquinolones; D007939:Leukemia L1210 / Q000469:parasitology; D051379:Mice; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism; D059004:Topoisomerase I Inhibitors; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects* / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011759:Pyrrolidines; D059004:Topoisomerase I Inhibitors; D014344:Trypanocidal Agents; D004247:DNA; D013936:Thymidine