Half-Sandwich Arene Ruthenium(II) and Osmium(II) Thiosemicarbazone Complexes: Solution Behavior and Antiproliferative Activity

被引:72
作者
Gatti, Anna [1 ,2 ,3 ]
Habtemariam, Abraha [3 ]
Romero-Canelon, Isolda [3 ,4 ]
Song, Ji-Inn [3 ]
Heer, Bindy [3 ]
Clarkson, Guy J. [3 ]
Rogolino, Dominga [1 ,2 ]
Sadler, Peter J. [3 ]
Carcelli, Mauro [1 ,2 ]
机构
[1] Univ Parma, Dipartimento Sci Chim Vita & Sostenibilita Ambien, Parco Area Sci 11-A, I-43124 Parma, Italy
[2] Univ Parma, CIRCMSB, Parco Area Sci 11-A, I-43124 Parma, Italy
[3] Univ Warwick, Dept Chem, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England
[4] Univ Birmingham, Sch Pharm, Birmingham B15 2TT, W Midlands, England
基金
英国工程与自然科学研究理事会; 英国惠康基金;
关键词
ANTICANCER ACTIVITY; ORGANOMETALLIC COMPLEXES; METASTASIS SUPPRESSOR; BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; REGULATED GENE-1; IRON CHELATORS; X-RAY; POTENT; DRUGS;
D O I
10.1021/acs.organomet.7b00875
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
We report the synthesis, characterization, and antiproliferative activity of organo-osmium(II) and organoruthenium(II) half-sandwich complexes [(eta(5)-p-cym)Os(L)Cl]-Cl (1 and 2) and [(eta(5)-p-cym)Ru(L)Cl]Cl (3 and 4), where L = N-(2-hydroxy)-3-methoxybenzylidenethiosemicarbazide (L1) or N-(2,3-dihydroxybenzylidene)-3-phenylthiosemicarbazide (L2), respectively. X-ray crystallography showed that all four complexes possess half-sandwich pseudo-octahedral "three-legged piano-stool" structures, with a neutral N,S-chelating thiosemicarbazone ligand and a terminal chloride occupying three coordination positions. In methanol, E/Z isomerization of the coordinated thiosemicarbazone ligand was observed, while in an aprotic solvent like acetone, partial dissociation of the ligand occurs, reaching complete displacement in a more coordinating solvent like DMSO. In general, the complexes exhibited good activity toward A2780 ovarian, A2780Cis cisplatin-resistant ovarian, AS49 lung, HCT116 colon, and PC3 prostate cancer cells. In particular, ruthenium complex 3 does not present cross-resistance with the clinical drug cisplatin in the A2780 human ovarian cancer cell line. The complexes were more active than the free thiosemicarbazone ligands, especially in A549 and HCT116 cells with potency improvements of up to 20-fold between organic ligand L1 and ruthenium complex 1.
引用
收藏
页码:891 / 899
页数:9
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