High in vivo antitumor activity of cobalt oxoisoaporphine complexes by targeting G-quadruplex DNA, telomerase and disrupting mitochondrial functions

作者：Qin, Qi-Pin; Qin, Jiao-Lan; Meng, Ting; Lin, Wan-Hua; Zhang, Chuan-Hui; Wei, Zu-Zhuang; Chen, Jia-Nian; Liu, Yan-Cheng; Liang, Hong; Chen, Zhen-Feng^*

来源：European Journal of Medicinal Chemistry, 2016, 124: 380-392.

DOI：10.1016/j.ejmech.2016.08.063

• Cobalt complex
• Oxoisoaporphine
• G4
• Antitumor mechanism
• Telomerase

Two G-quadruplex ligands: [Co(H-L-a)(2)Cl-2] (Co1) and [Co(L-b)(2)][CoCl4]center dot 2H(2)O (Co2) have been synthesized and characterized. Two cobalt oxoisoaporphine complexes exhibited selective cytotoxicity to SK-OV-3/DDP cells than for HL-7702 cells. Cytotoxic mechanism studies indicated that both Co1 and Co2 were telomerase inhibitor targeting c-myc, telomere, and bcl-2 G4s, and triggering cell senescence and apoptosis, which caused S phase arrest. They also induced mitochondrial dysfunction. The better antitumor activity of Co2, which should be correlated with a moiety of 2-[5-(2-pyridiny1)-1H-pyrrol-2-yl]pyridine in the L-b. Importantly, Co2 at high doses showed at least the same level of tumor growth inhibition efficacy compared to that of cisplatin, and better in vivo safety profile.

• 出版日期2016-11-29
• 单位广西师范大学