Konkankit Chilaluck C, King A Paden, Knopf Kevin M, Southard Teresa L, Wilson Justin J
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, United States.
ACS Med Chem Lett. 2019 Apr 23;10(5):822-827. doi: 10.1021/acsmedchemlett.9b00128. eCollection 2019 May 9.
The rhenium(I) complex -[Re(CO)(2,9-dimethyl-1,10-phenanthroline)(OH)] () was previously shown to exhibit potent in vitro anticancer activity in a manner distinct from conventional platinum-based drugs ( , , 14302-14314). In this study, we report further efforts to explore its aqueous speciation and antitumor activity. The cellular uptake of was measured in A2780 and cisplatin-resistant A2780CP70 ovarian cancer cells by inductively coupled plasma mass spectrometry, revealing similar uptake efficiency in both cell lines. High accumulation in the mitochondria was observed, contradicting prior fluorescence microscopy studies. The luminescence of is highly dependent on pH and coordination environment, making fluorescence microscopy somewhat unreliable for determining compound localization. The in vivo anticancer activity of was evaluated in mice bearing patient-derived ovarian cancer tumor xenografts. These studies conclusively show that is capable of inhibiting tumor growth, providing further credibility for the use of these compounds as anticancer agents.
先前的研究表明，铼（I）配合物-[Re(CO)(2,9-二甲基-1,10-菲咯啉)(OH)]（）以一种不同于传统铂类药物的方式展现出强大的体外抗癌活性（，，14302 - 14314）。在本研究中，我们报告了进一步探索其水相形态和抗肿瘤活性的工作。通过电感耦合等离子体质谱法测定了在A2780和顺铂耐药的A2780CP70卵巢癌细胞中对的细胞摄取情况，结果显示两种细胞系中的摄取效率相似。观察到在线粒体中有高积累，这与先前的荧光显微镜研究结果相矛盾。的发光高度依赖于pH值和配位环境，这使得荧光显微镜在确定化合物定位方面有些不可靠。在携带患者来源的卵巢癌肿瘤异种移植模型的小鼠中评估了的体内抗癌活性。这些研究确凿地表明能够抑制肿瘤生长，为将这些化合物用作抗癌药物提供了进一步的可信度。
