†Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
‡Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
J Med Chem. 2015 May 28;58(10):4339-47. doi: 10.1021/acs.jmedchem.5b00403. Epub 2015 May 15.
New ruthenium(II) and iron(II) organometallic compounds of general formula [(η(5)-C5H5)M(PP)Lc][PF6], bearing carbohydrate derivative ligands (Lc), were prepared and fully characterized and the crystal structures of five of those compounds were determined by X-ray diffraction studies. Cell viability of colon cancer HCT116 cell line was determined for a total of 23 organometallic compounds and SAR's data analysis within this library showed an interesting dependency of the cytotoxic activity on the carbohydrate moiety, linker, phosphane coligands, and metal center. More importantly, two compounds, 14Ru and 18Ru, matched oxaliplatin IC50 (0.45 μM), the standard metallodrug used in CC chemotherapeutics, and our leading compound 14Ru was shown to be significantly more cytotoxic than oxaliplatin to HCT116 cells, triggering higher levels of caspase-3 and -7 activity and apoptosis in a dose-dependent manner.
新型钌(II)和铁(II)有机金属化合物，通式为[(η(5)-C5H5)M(PP)Lc][PF6]，具有碳水化合物衍生物配体 (Lc)，已被制备并进行了全面的表征，其中五个化合物的晶体结构已通过 X 射线衍射研究确定。总共对 23 种有机金属化合物进行了结肠癌细胞 HCT116 细胞活力的测定，对该库中的 SAR 数据分析表明，细胞毒性活性与碳水化合物部分、连接体、膦配体和金属中心密切相关。更重要的是，两种化合物 14Ru 和 18Ru 的 IC50（0.45 μM）与奥沙利铂相匹配，奥沙利铂是 CC 化疗中使用的标准金属药物，而我们的先导化合物 14Ru 对 HCT116 细胞的细胞毒性明显高于奥沙利铂，以剂量依赖的方式引发更高水平的 caspase-3 和 -7 活性和细胞凋亡。
