Antitrypanosomal activity of fluoroquinolones.
Six fluoroquinolones presently in clinical use and four investigational tetracyclic fluoroquinolones were tested for in vitro activity against bloodstream-form Trypanosoma brucei brucei. All compounds had measurable activity, but the tetracyclic analogs were most potent, with 50% effective concentrations in the low micromolar range. In general, trypanosomes were more susceptible than L1210 leukemia cells. Consistent with the notion that they target type II topoisomerase in trypanosomes, the fluoroquinolones promote the formation of protein-DNA covalent complexes.
Nenortas
E
E
Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.
Burri
C
C
Shapiro
T A
TA
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity; D018736:DNA Adducts / Q000096:biosynthesis; D016054:DNA, Protozoan / Q000378:metabolism; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D015366:Pefloxacin / Q000494:pharmacology; D015800:Protozoan Proteins / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000633:toxicity; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D018736:DNA Adducts; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D015366:Pefloxacin