Antitrypanosomal activities of fluoroquinolones with pyrrolidinyl substitutions.
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.
Nenortas
Elizabeth
E
Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Kulikowicz
Tomasz
T
Burri
Christian
C
Shapiro
Theresa A
TA
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
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011759:Pyrrolidines; D059004:Topoisomerase I Inhibitors; D014344:Trypanocidal Agents; D004247:DNA; D013936:Thymidine