具有汉防己甲素衍生物的发光铂（II）配合物的高体外和体内抗肿瘤活性。
High in vitro and in vivo antitumor activities of luminecent platinum(II) complexes with jatrorrhizine derivatives.
机构信息
Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin, 537000, PR China; 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.
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; Department of Chemistry, Guilin Normal College, 9 Feihu Road, Guilin, 541001, China.
出版信息
Eur J Med Chem. 2019 Dec 1;183:111727. doi: 10.1016/j.ejmech.2019.111727. Epub 2019 Sep 21.
Two highly active anticancer Pt(II) complexes, [Pt(Jat1)Cl]Cl (Pt1) and [Pt(Jat2)Cl]Cl (Pt2), containing jatrorrhizine derivative ligands (Jat1 and Jat2) are described. Cell intake study showed high accumulation in cell nuclear fraction. Pt1 and Pt2 exhibited high selectivity for HeLa cancer cells (IC = 15.01 ± 1.05 nM and 1.00 ± 0.17 nM) comparing with HL-7702 normal cells (IC > 150 μM), by targeting p53 and telomerase. Pt2 containing Jat2 ligand was more potent and showed high selectivity for telomerase. It also caused mitochondria and DNA damage, sub-G1 phase arrest, and a high rate of cell apoptosis at the low dose of 1.00 nM. The HeLa tumor inhibition rate (TIR) of Pt2 was 48.8%, which was even higher than cisplatin (35.2%). In addition, Pt2 displayed green luminescent property and potent telomerase inhibition. Our findings demonstrated the promising development of platinum(II) complexes containing jatrorrhizine derivatives as novel Pt-based anti-cancer agents.
两种高活性的抗癌 Pt(II) 配合物，[Pt(Jat1)Cl]Cl (Pt1) 和 [Pt(Jat2)Cl]Cl (Pt2)，含有小檗碱衍生物配体 (Jat1 和 Jat2)。细胞摄取研究表明，它们在细胞核部分高度积累。Pt1 和 Pt2 对 HeLa 癌细胞（IC = 15.01 ± 1.05 nM 和 1.00 ± 0.17 nM）具有高选择性，而对 HL-7702 正常细胞（IC > 150 μM）则没有选择性，这是通过靶向 p53 和端粒酶实现的。含有 Jat2 配体的 Pt2 更有效，对端粒酶具有高选择性。它还能引起线粒体和 DNA 损伤，在低剂量 1.00 nM 时，使细胞停滞在 sub-G1 期，并导致高比例的细胞凋亡。Pt2 的 HeLa 肿瘤抑制率 (TIR) 为 48.8%，甚至高于顺铂 (35.2%)。此外，Pt2 还具有绿色发光特性和强大的端粒酶抑制作用。我们的研究结果表明，含有小檗碱衍生物的铂(II) 配合物具有作为新型基于铂的抗癌药物的广阔发展前景。
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