期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 49, 期 23, 页码 6858-6868出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm060596m
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We report structure-activity relationships for organometallic Ru-II complexes of the type [( eta(6)-arene) Ru-( XY) Cl] Z, where XY is an N, N-( diamine), N, O-( e. g., amino acidate), or O,O- ( e. g., beta-diketonate) chelating ligand, the arene ranges from benzene derivatives to fused polycyclic hydrocarbons, and Z is usually PF6. The X-ray structures of 13 complexes are reported. All have the characteristic piano-stool geometry. The complexes most active toward A2780 human ovarian cancer cells contained XY) ethylenediamine ( en) and extended polycyclic arenes. Complexes with polar substituents on the arene or XY) bipyridyl derivatives exhibited reduced activity. The activity of the O, O- chelated complexes depended strongly on the substituents and on the arene. For arene) p-cymene, XY) amino acidate complexes were inactive. Complexes were not cross-resistant with cisplatin, and cross-resistance to Adriamycin was circumvented by replacing XY) en with 1,2-phenylenediamine. Some complexes were also active against colon, pancreatic, and lung cancer cells.
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