Research Papers:

Chiral platinum (II)-4-(2,3-dihydroxypropyl)- formamide oxo-aporphine (FOA) complexes promote tumor cells apoptosis by directly targeting G-quadruplex DNA in vitro and in vivo

Qi-Pin Qin, Jiao-Lan Qin, Ming Chen, Yu-Lan Li, Ting Meng, Jie Zhou, Hong Liang _ and Zhen-Feng Chen

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Oncotarget. 2017; 8:61982-61997. https://doi.org/10.18632/oncotarget.18778

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Qi-Pin Qin1, Jiao-Lan Qin1, Ming Chen1, Yu-Lan Li1, Ting Meng1, Jie Zhou1, Hong Liang1 and Zhen-Feng Chen1

1State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin 541004, P. R. China

Correspondence to:

Hong Liang, email: [email protected]

Zhen-Feng Chen, email: [email protected]

Keywords: chiral platinum(II) complex, oxoaporphine, G-quadruplex DNA, telomerase, antitumor activity

Received: March 01, 2017    Accepted: May 06, 2017    Published: June 28, 2017


Three platinum(II) complexes, 4 (LC-004), 5 (LC-005), and 6 (LC-006), with the chiral FOA ligands R/S-(±)-FOA (1), R-(+)-FOA (2) and S-(–)-FOA (3), respectively, were synthesized and characterized. As potential anti-tumor agents, these complexes show higher cytotoxicity to BEL-7404 cells than the HL-7702 normal cells. They are potential telomerase inhibitors that target c-myc and human telomeric G-quadruplex DNA. Compared to complexes 4 and 5, 6 exhibited higher binding affinities towards telomeric, c-myc G-quadruplex DNA and caspase-3/9, thereby inducing senescence and apoptosis to a greater extent in tumor cells. Moreover, our in vivo studies showed that complex 6 can effectively inhibit tumor growth in the BEL-7404 and BEL-7402 xenograft mouse models and is less toxic than 5-fluorouracil and cisplatin. The effective inhibition of tumor growth is attributed to its interactions with 53BP1, TRF1, c-myc, TRF2, and hTERT. Thus, complex 6 can serve as a novel lead compound and a potential drug candidate for anticancer chemotherapy.

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