Triazolyl Ru-II, Rh-III, Os-II, and Ir-III Complexes as Potential Anticancer Agents: Synthesis, Structure Elucidation, Cytotoxicity, and DNA Model Interaction Studies

摘要

Novel conjugated ruthenium(II), rhodium-(III), and iridium(III) organometallic complexes of triazoles 1 and 2 synthesized and evaluated for anticancer activity against cervical (HeLa), kidney (HEK293), nonsmall lung cancer (A549), and leukemia (MT4) cancer cell lines are reported herein. The complexes are kappa(2)-N,C coordinated and have the formula [ML(Ar)Cl] (where L is 1-benzyl-4-phenyl-1H-1,2,3-triazole for 1 and 1-benzyl-4-hydroxymethyl-1H1,2,3-triazole for 2, Ar is p-cymene for Run and Os-II and Cp* for Rhin and Ir-III, and M is metal). NMR studies, including HMBC and NOESY, were employed to unambiguously elucidate their structures and provide their conformational information in solution. Single-crystal X-ray diffraction data have been used to establish the solid-state structures of selected complexes, which further confirm the structural elucidation by NMR Dynamic NMR studies, such as differential transferred NOE, have been employed to distinguish between isomers 1a_I and 1a_II of ruthenium(II) complexes of triazole 1. The rhodium(III) (1b) and iridium(III) (1c) complexes exhibited good cytotoxic activities (CC50 = 4-6 mu M) comparable to that of the drug auranofin against lung cancer A549 cell lines (CC50 = 4.69 mu M). While triazole 1 based ruthenium(II) (1a) and osmium(II) (1d) complexes displayed modest anticancer activities against HeLa and HEK293 cell lines, the analogous rhodium(III) and iridium(III) complexes exhibited good potential (CC50 = 9-54 mu M versus auranofin (3-9 mu M)) against these cancer cell lines. Insightful NMR studies on the interaction between the DNA model guanosine 5'-GMP and the complexes 1b,c reveal a possible mode of action of the aquated complexes involving carbenylation with DNA bases or purines through the triazolyl proton H-5. From the findings, these complexes could possibly confer their cytotoxic activities through intercalation with the DNA of pathological cells. Therefore, carbenylation of the triazolylrhodium(III) and