Qin Qi-Pin, Meng Ting, Tan Ming-Xiong, Liu Yan-Cheng, Luo Xu-Jian, Zou Bi-Qun, Liang Hong
Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin, Guangxi 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.
Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin, Guangxi 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.
Eur J Med Chem. 2018 Jan 1;143:1387-1395. doi: 10.1016/j.ejmech.2017.10.035. Epub 2017 Oct 16.
There iridium(III) complexes, [Ir(3-MeO-Phtpy)Cl] (1), [Ir(2-MeO-Phtpy)Cl] (2) and [Ir(4-MeO-Phtpy)Cl] (3) with 4'-(3-methoxyphenyl)-2,2':6',2″-terpyridine (3-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2″-terpyridine (2-MeO-Phtpy) and 4'-(4-methoxyphenyl)-2,2':6',2″-terpyridine (4-MeO-Phtpy) as ligands, respectively, were synthesized and evaluated for their antiproliferative activities. In these complexes, the iridium(III) center adopts a six-coordinate distorted octahedral geometry. Among them, complex 1 exhibited the most potent activity, with IC values of 3.19-27.77 μM against four cancer cell lines (BEL-7404, Hep-G2, NCI-H460 and MGC80-3 cells). Cellular mechanism studies suggested that complexes 1-3 directly targeted c-myc promoter elements and inhibited the telomerase activity. In addition, complexes 1-3 may trigger cell apoptosis via a mitochondrial dysfunction pathway. We postulated that the difference in the in vitro antitumor activities of complexes 1-3 is mainly dependent on the position of the methoxy group on the phenyl ring of the iridium ligand.
合成了分别以4'-(3-甲氧基苯基)-2,2':6',2″-三联吡啶（3-MeO-Phtpy）、4'-(2-甲氧基苯基)-2,2':6',2″-三联吡啶（2-MeO-Phtpy）和4'-(4-甲氧基苯基)-2,2':6',2″-三联吡啶（4-MeO-Phtpy）为配体的铱(III)配合物[Ir(3-MeO-Phtpy)Cl]（1）、[Ir(2-MeO-Phtpy)Cl]（2）和[Ir(4-MeO-Phtpy)Cl]（3），并对其增殖抑制活性进行了评估。在这些配合物中，铱(III)中心采用六配位扭曲八面体几何构型。其中，配合物1表现出最强的活性，对四种癌细胞系（BEL-7404、Hep-G2、NCI-H460和MGC80-3细胞）的IC值为3.19 - 27.77 μM。细胞机制研究表明，配合物1 - 3直接靶向c-myc启动子元件并抑制端粒酶活性。此外，配合物1 - 3可能通过线粒体功能障碍途径触发细胞凋亡。我们推测，配合物1 - 3体外抗肿瘤活性的差异主要取决于铱配体苯环上甲氧基的位置。
