title: Synthesis and evaluation of 1-cyclopropyl-2-thioalkyl-8-methoxy fluoroquinolones.
abstract: Novel fluoroquinolone derivatives substituted with a 2-thioalkyl moiety, with and without a concomitant 3-carboxylate group, were synthesized to evaluate the effect of C-2 thioalkyl substituents on gyrase binding and inhibition. The presence of a 2-thioalkyl group universally decreased activity as compared to parent fluoroquinolones. However, with derivatives of moxifloxacin the presence of either a 2-thioalkyl group or a 3-carboxylate moiety increased activity over the 2,3-unsubstituted derivative. Energy minimization of structures provides an explanation for relative activities of fluoroquinolones having a C-2 thio moiety.
authors.affiliation: Division of Medicinal and Natural Products Chemistry, University of Iowa College of Pharmacy, Iowa City, IA 52242, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Marks
authors.forename: Muhammad
authors.initials: M
authors.lastname: Malik
authors.forename: Arkady
authors.initials: A
authors.lastname: Mustaev
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiasa
authors.forename: Karl
authors.initials: K
authors.lastname: Drlica
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kerns
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000737:chemistry; D027081:DNA Gyrase / Q000378:metabolism; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry; D059005:Topoisomerase II Inhibitors
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase; D000077266:Moxifloxacin