title: [Synthesis and antitumor activity of C3 heterocyclic-substituted fluoroquinolone derivatives (I): ciprofloxacin aminothiodiazole Schiff-bases].
abstract: To discover a novel antitumor lead compound derived from fluoroquinolone, C3 carboxyl group of ciprofloxacin (1) was replaced with heterocyclic ring to form cyclopropyl fluoroquinolone aminothiadiazole scaffold (2), then reacted with aromatic aldehydes to give the Schiff bases compounds (3a-3j). The structures of new compounds were characterized by element analysis and spectral data, and their in vitro antitumor activity against SMMC-7721, HL60 and L1210 cell lines was evaluated by MTT assay via the respective IC50 values. The bioactive assay showed that eleven thiadiazole-substituted ciprofloxacin derivatives displayed potential cytotoxicity against the tested cancer cell lines, where the IC50 values of compounds 3d and 3f reached micromolar concentration. Therefore, the C3 carboxyl group of fluoroquinolone is not necessary to antitumor activity. Functionally modified heterocycle-substituted fluoroquinolone as potent antitumor lead compound is valuable for further study.
authors.affiliation: Institute of Pharmacy, Henan University, Kaifeng 475004, China. hgqxy@sina.com.cn
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Hu
authors.forename: Xiao-Kui
authors.initials: XK
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Song-Qiang
authors.initials: SQ
authors.lastname: Xie
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Huang
authors.forename: Hui-Bin
authors.initials: HB
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D012545:Schiff Bases / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D012545:Schiff Bases; D002939:Ciprofloxacin