Platinum(ii) complexes with rutaecarpine and tryptanthrin derivatives induce apoptosis by inhibiting telomerase activity and disrupting mitochondrial function

被引：12
作者：
Qin, Qi-Pin [1 ,4 ]
Zou, Bi-Qun [1 ,3 ,4 ]
Hu, Fei-Long [2 ]
Huang, Guo-Bao [1 ]
Wang, Shu-Long [1 ,4 ]
Gu, Yun-Qiong [1 ,4 ]
Tan, Ming-Xiong [1 ]
机构：
[1] Yulin Normal Univ, Sch Chem & Food Sci, Guangxi Key Lab Agr Resources Chem & Biotechnol, 1303 Jiaoyudong Rd, Yulin 537000, Peoples R China
[2] Guangxi Univ Nationalities, Guangxi Key Lab Chem & Engn Forest Prod, Nanning 530006, Peoples R China
[3] Guilin Normal Coll, Dept Chem, 21 Xinyi Rd, Gulin 541001, Peoples R China
[4] Guangxi Normal Univ, Sch Chem & Pharm, State Key Lab Chem & Mol Engn Med Resources, 15 Yucai Rd, Guilin 541004, Peoples R China
来源：
MEDCHEMCOMM | 2018年 / 9卷 / 10期
基金：
中国国家自然科学基金;
关键词：
G-QUADRUPLEX DNA; MYC G-QUADRUPLEX; TUMOR-CELL APOPTOSIS; ONCOGENE C-MYC; RUTHENIUM(II) COMPLEXES; BIOLOGICAL EVALUATION; DOWN-REGULATION; IN-VITRO; ALKALOIDS RUTAECARPINE; POLYPYRIDYL COMPLEXES;
D O I：
10.1039/c8md00247a
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Four new platinum(ii) complexes, [Pt(Rut)(DMSO)Cl-2] (Rut-Pt), [Pt(Try)(DMSO)Cl-2] (Try-Pt), [Pt(ITry)(DMSO)Cl-2] (ITry-Pt) and [Pt(BrTry)(DMSO)Cl-2] (BrTry-Pt), with rutaecarpine (Rut), tryptanthrin (Try), 8-iodine-tryptanthrin (ITry) and 8-bromo-tryptanthrin (BrTry) as ligands were synthesized and fully characterized. In these complexes, the platinum(ii) adopts a four-coordinated square planar geometry. The inhibitory activity evaluated by the MTT assay showed that BrTry-Pt (IC50 = of 0.21 +/- 0.25 M) could inhibit the growth of T-24 tumor cells (human bladder cancer cell line) more so than the other three complexes. In addition, all of these Pt complexes exhibited low toxicity against non-cancerous HL-7702 cells. BrTry-Pt induced cell cycle arrest in the S phase, leading to the down-regulation of cyclin A and CDK2 proteins. BrTry-Pt acts as a telomerase inhibitor targeting the c-myc promoter. In addition, BrTry-Pt also caused mitochondrial dysfunction. Importantly, the in vitro anticancer activity of BrTry-Pt was higher than those of Rut-Pt, Try-Pt and ITry-Pt, and it was more selective for T-24 cells than for non-cancerous HL-7702 cells.
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收藏
页码：1639 / 1648
页数：10
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