title: Ciprofloxacin containing Mannich base and its copper complex induce antitumor activity via different mechanism of action.
abstract: The Mannich base containing ciprofloxacin and kojic acid structural units was prepared and evaluated in antitumor activity. The enhancement in antitumor activity was observed both from the Mannich base (IC(50): 103.3±5.0 µM for HepG2, 87.9±8.0 µM for HCT-116 cell) and its copper complex (IC(50): 11.5±1.8 µM for HepG2, 44.4±2.5 µM for HCT-116 cell) compared to the ciprofloxacin and kojic acid. The mechanistic studies via RT-PCR, cell cycle analysis, mitochondrial membrane potential measurement, inhibition of topoisomerase and molecular docking indicated that there is a different molecular mechanism between the Mannich base and its copper complex. The cytotoxicity of the Mannich base was involved in apoptosis, cell cycle arrest, depolarization of mitochondrial membrane and weaker topoisomerase II inhibition, but the copper complex exerted its cytotoxicity mainly through dual topoisomerase inhibition, especially stabilizing the intermediate of cleavage DNA-topoisomerase complex.
authors.affiliation: Department of Molecular Biology and Biochemistry, Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Molecular Biology and Biochemistry, Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Clinical Skill Training Center, Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Molecular Biology and Biochemistry, Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Youxun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Surgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Surgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Molecular Biology and Biochemistry, Xinxiang Medical University, Xinxiang, Henan, P.R. China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000737:chemistry; D003300:Copper / Q000008:administration & dosage* / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D008352:Mannich Bases / Q000008:administration & dosage / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011753:Pyrones / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D008352:Mannich Bases; D011753:Pyrones; D002939:Ciprofloxacin; C011890:kojic acid; D003300:Copper