title: Synthesis and antimycobacterial evaluation of certain fluoroquinolone derivatives.
abstract: A number of fluoroquinolone derivatives were synthesized and evaluated for antimycobacterial activity. Preliminary results are (1) for 1-aryl fluoroquinolones, 1-(4-nitrophenyl) derivatives were inactive while their 1-(2-fluoro-4-nitrophenyl) counterparts were active anti-TB agents (3a vs 4a; 3b vs 4b) indicated the fluoro substituent at C-2 position is important. For the 1-(2-fluoro-4-nitrophenyl)quinolones, 7-piperidinyl derivative 4a and 7-(3,5-dimethylpiperazinyl) derivative 4e, which exhibited 97% and 98% inhibition, respectively, were more active than their 7-morpholinyl, 7-(4-methylpiperazinyl) and 7-piperazinyl congeners, 4b,4c and 4d, respectively. In addition, 7-[4-(8-hydroxyquinolin-2-ylmethyl)piperazin-1-yl] derivative 9d exhibited 44% inhibition on the growth of Mycobacterium tuberculosis while its 7-(4-methylpiperazin-1-yl) counterpart 3c was inactive implied the metal-chelating 8-hydroxyquinoline moiety was capable of enhancing the anti-TB activity, (2) for the bifunctional fluoroquinolone-hydroxyquinoline complexes, ciprofloxacin and ofloxacine derivatives, which exhibited the same anti-TB activity (98% inhibition), are more potent than norfloxacin counterpart, which in turn is more potent than 1-aryl congeners (9b, 9c>9a>9d, 9e).
authors.affiliation: Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Yue-Ling
authors.initials: YL
authors.lastname: Zhao
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Jia-Yuh
authors.initials: JY
authors.lastname: Sheu
authors.forename: I-Li
authors.initials: IL
authors.lastname: Chen
authors.forename: Tai-Chi
authors.initials: TC
authors.lastname: Wang
authors.forename: Cherng-Chyi
authors.initials: CC
authors.lastname: Tzeng
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002614:Chelating Agents; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D015125:Oxyquinoline; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D002614:Chelating Agents; D024841:Fluoroquinolones; D015125:Oxyquinoline