Study summary · research use only
Degradation of bidentate-coordinated platinum(II)-based DNA intercalators by reduced L-glutathione
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This is a chemistry study with in vitro cytotoxicity components (no whole organism). The authors examined the interaction of four platinum(II)-based DNA intercalator complexes (labeled 1-4, including 56MESS, 5MESS, 56MERR, and 56MEEN) with reduced L-glutathione and L-methionine. Both thiols degraded all four complexes, mainly by displacing the ancillary ligand and forming a doubly bridged dinuclear complex. Degradation half-life with methionine was reported as greater than 7 days, described as not biologically relevant. Degradation by glutathione showed an inverse correlation to cytotoxicity: the least active complex 4 (glutathione t1/2: 20 h) degraded fastest, followed by 3 (31 h), 2 (40 h), and 1 (68 h). The major degradation product showed no cytotoxicity. The authors report that once glutathione-bound the complexes did not bind guanosine, and that cucurbit[n]uril encapsulation could stop degradation.
Abstract
We have examined the interaction of [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] (2+) (1, 56MESS), [(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] (2+) (2, 5MESS), [(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)platinum(II)] (2+) (3, 56MERR), and [(5,6-dimethyl-1,10-phenanthroline)(ethylenediamine)platinum(II)] (2+) (4, 56MEEN) with reduced L-glutathione and L-methionine. Both thiols degrade all four complexes, mainly by displacing the ancillary ligand and forming a doubly bridged dinuclear complex. The degradation half-life of all the complexes with methionine is >7 days, indicating that these reactions are not biologically relevant. The rate of degradation by glutathione appears to be particularly important and shows an inverse correlation to cytotoxicity. The least active complex, 4 (t 1/2 glutathione: 20 h), degrades fastest, followed by 3 (31 h), 2 (40 h), and 1 (68 h). The major degradation product, [bis-mu-{reduced L-glutathione}bis{5,6-dimethyl-1,10-phenanthroline}bis{platinum(II)}] (2+) (5, 56MEGL), displays no cytotoxicity and is excluded as the source of the anticancer activity. Once bound by glutathione, these metal complexes do not then form coordinate bonds with guanosine. Partial encapsulation of the complexes within cucurbit[n]urils is able to stop the degradation process.
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