期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 51, 期 4, 页码 798-808出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm701146c
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Monocationic hydrophilic complexes [Cu(thp)(4)](+) 3 and [Cu(bhpe)(2)](+) 4 were synthesized by ligand exchange reactions starting from the labile [Cu(CH3CN)(4)][PF6] precursor in the presence of an excess of the relevant hydrophilic phosphine. Complexes 3 and 4 were tested against a panel of several human tumor cell lines., Complex 3 has been shown to be about L order of magnitude more cytotoxic than cisplatin. Chemosensitivity tests performed on cisplatin and multidrug resistance phenotypes suggested that complex 3 acts via a different mechanism of action than the reference drug. Different short-term proliferation assays suggested that lysosomal damage is an early cellular event associated with complex 3 cytotoxicity, probably mediated by an increased production of reactive oxygen species. Cytological stains and flow cytometric analyses indicated that the phosphine copper(I) complex is able to inhibit the growth of tumor cells via G2/M cell cycle arrest and paraptosis accompanied with the loss of mitochondrial transmembrane potential.
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