title: [Synthesis and antitumor activity of fluoroquinolon-3-yl-s-triazole sulfide ketones and their derivatives from ciprofloxacin].
abstract: To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Ni
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yan
authors.forename: Shu-min
authors.initials: SM
authors.lastname: Wu
authors.forename: Yu-suo
authors.initials: YS
authors.lastname: Xie
authors.forename: Liu-zhou
authors.initials: LZ
authors.lastname: Gao
authors.forename: Ying-jie
authors.initials: YJ
authors.lastname: Liu
authors.forename: Wen-long
authors.initials: WL
authors.lastname: Huang
authors.forename: Guo-qiang
authors.initials: GQ
authors.lastname: Hu
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002939:Ciprofloxacin / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007659:Ketones; D013440:Sulfides; D014230:Triazoles; D002939:Ciprofloxacin; D004317:Doxorubicin