Synthesis and evaluation of new polynuclear organometallic Ru(II), Rh(III) and Ir(III) pyridyl ester complexes as in vitro antiparasitic and antitumor agents

被引:56
作者
Chellan, Prinessa [1 ]
Land, Kirkwood M. [2 ]
Shokar, Ajit [2 ]
Au, Aaron [2 ]
An, Seung Hwan [2 ]
Taylor, Dale [3 ]
Smith, Peter J. [3 ]
Riedel, Tina [4 ]
Dyson, Paul J. [4 ]
Chibale, Kelly [1 ]
Smith, Gregory S. [1 ]
机构
[1] Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa
[2] Univ Pacific, Dept Biol Sci, Stockton, CA 95211 USA
[3] Univ Cape Town, Dept Med, Div Pharmacol, OMB,Groote Schuur Hosp, ZA-7925 Observatory, South Africa
[4] Ecole Polytech Fed Lausanne, Inst Sci & Ingn Chim, CH-1015 Lausanne, Switzerland
基金
新加坡国家研究基金会;
关键词
ARENE RUTHENIUM COMPLEXES; DRUG-DELIVERY; ANTICANCER ACTIVITY; STRUCTURAL-CHARACTERIZATION; PLASMODIUM-FALCIPARUM; ANTIMALARIAL ACTIVITY; POLYESTER DENDRIMERS; IRIDIUM COMPLEXES; RHODIUM; DERIVATIVES;
D O I
10.1039/c3dt52090k
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
New polynuclear organometallic Platinum Group Metal (PGM) complexes containing di- and tripyridyl ester ligands have been synthesised and characterised using analytical and spectroscopic techniques including H-1, C-13 NMR and infrared spectroscopy. Reaction of these polypyridyl ester ligands with either [Ru(p-cymene)Cl-2](2), [Rh(C5Me5)Cl-2](2) or [Ir(C5Me5)Cl-2](2) dimers yielded the corresponding di- or trinuclear organometallic complexes. The polyaromatic ester ligands act as monodentate donors to each metal centre and this coordination mode was confirmed upon elucidation of the molecular structures for two of the dinuclear complexes. The di- and trinuclear PGM complexes synthesized were evaluated for inhibitory effects on the human protozoal parasites Plasmodium falciparum strain NF54 (chloroquine sensitive), Trichomonas vaginalis strain G3 and the human ovarian cancer cell lines, A2780 (cisplatin-sensitive) and A2780cisR (cisplatin-resistant) cell lines. All of the complexes were observed to have moderate to high antiplasmodial activities and the compounds with the best activities were evaluated for their ability to inhibit formation of synthetic hemozoin in a cell free medium. The in vitro antitumor evaluation of these complexes revealed that the trinuclear pyridyl ester complexes demonstrated moderate activities against the two tumor cell lines and were also less toxic to model non-tumorous cells.
引用
收藏
页码:513 / 526
页数:14
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