[Synthesis and antitumor activity of C3 heterocyclic-substituted fluoroquinolone derivatives (I): ciprofloxacin aminothiodiazole Schiff-bases].
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.
Hu
Guo-Qiang
GQ
Institute of Pharmacy, Henan University, Kaifeng 475004, China. hgqxy@sina.com.cn
Wu
Xiao-Kui
XK
Wang
Xin
X
Zhang
Zhi-Qiang
ZQ
Xie
Song-Qiang
SQ
Huang
Wen-Long
WL
Zhang
Hui-Bin
HB
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
D000970:Antineoplastic Agents; D012545:Schiff Bases; D002939:Ciprofloxacin