Ciprofloxacin containing Mannich base and its copper complex induce antitumor activity via different mechanism of action

Fu,Yun; Yang,Yingli; Zhou,Sufeng; Liu,Youxun; Yuan,Yanbin; Li,Shaoshan; Li,Changzheng

doi:10.3892/ijo.2014.2611

Ciprofloxacin containing Mannich base and its copper complex induce antitumor activity via different mechanism of action

Authors:
- Yun Fu
- Yingli Yang
- Sufeng Zhou
- Youxun Liu
- Yanbin Yuan
- Shaoshan Li
- Changzheng Li
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Affiliations: Department of Molecular Biology and Biochemistry, Xinxiang Medical University, Xinxiang, Henan, P.R. China, Clinical Skill Training Center, Xinxiang Medical University, Xinxiang, Henan, P.R. China, Department of Surgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, P.R. China
Published online on: August 19, 2014 https://doi.org/10.3892/ijo.2014.2611
Pages: 2092-2100

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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 (IC50: 103.3±5.0 µM for HepG2, 87.9±8.0 µM for HCT-116 cell) and its copper complex (IC50: 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.

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