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Strong in vitro and in vivo cytotoxic effects of two platinum(II) complexes with cryptolepine derivatives

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Abstract

Two mononuclear Pt(II) compounds, [Pt(BQL1)Cl]Cl (BQL1-Pt) and [Pt(BQL2)Cl]Cl (BQL2-Pt), with [5-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-pentyl]-bis-pyridin-2-ylmethyl-amine (BQL1) and [9-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-nonyl]-bis-pyridin-2-ylmethyl-amine (BQL2), were prepared as new chemotypes for potential antitumor agents. In this study, the effects of cryptolepine derivatives in BQL1-Pt, 2,2′-dipicolylamine Pt(II) complex, and BQL2-Pt on cellular Pt(II) accumulation, cytotoxicity, and in vitro and in vivo antitumor activities against T-24 cancer cells and normal HL-7702 cells were evaluated. BQL1-Pt and BQL2-Pt displayed cytotoxic activities in the micromolar range (1.3 ± 0.1 and 0.2 ± 0.2 μM, respectively) on T-24 cancer cells; however, they did not exhibit any toxicity against HL-7702 cells. They triggered T-24 cell apoptosis through a mitochondrial dysfunction pathway. BQL1-Pt and BQL2-Pt prepared from the neutral BQL1 and BQL2 ligands with cryptolepine derivatives showed better antitumor activities than 2,2′-dipicolylamine. Furthermore, BQL2-Pt effectively inhibited the growth of bladder T-24 tumor in vivo. BQL2-Pt could be a potential therapeutic candidate for cancers.

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Acknowledgements

We thank the National Natural Science Foundation of China (21867017) and the Natural Science Foundation of Guangxi (2020GXNSFAA297077).

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  1. These authors contributed equally: Li-Qin Qin, Zu-Zhuang Wei

Authors and Affiliations

  1. College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin, 537000, PR China

    Li-Qin Qin, Lin Yang, Qi-Pin Qin, Jia-Jing Zeng & Ming-Xiong Tan

  2. School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou, 510006, PR China

    Zu-Zhuang Wei

  3. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin, 541004, PR China

    Qi-Pin Qin & Hong Liang

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Qin, LQ., Wei, ZZ., Yang, L. et al. Strong in vitro and in vivo cytotoxic effects of two platinum(II) complexes with cryptolepine derivatives. Med Chem Res 30, 1419–1426 (2021). https://doi.org/10.1007/s00044-021-02739-0

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