Interactions of Platinum Amine Compounds with Sulfur-Containing Biomolecules and Dna Fragments

Study of the reactions between platinum(II) complexes and l-methionine in the presence and absence of 5′-GMP

“…However, this is in agreement with the previous results [26]. Moreover, this results could be very important because Pt-sulfur (thioe- thers) adducts have been postulated to be a drug reservoir for platinum at DNA and may act as intermediates of platinum compounds and transform them into Pt-DNA adducts [8][9][10][11][12]. On the other hand, platinum complexes could be inactivated in the reactions with cysteine-rich proteins, like glutathione (GSH), or metallothionine (MT) [12] and could trap and deactivate the drug before it reaches its cellular target, DNA, to form intrastand cross-linked guanine bases, the likely cytotoxic adducts [27], see Scheme 1.…”

“…A conventional hypothesis is that sulfur containing nucleophiles initially bind to the platinum atom and then convert to platinum-DNA complexes, thermodynamically more stable products. Pt-sulfur (thioethers) adducts have been postulated to be a drug reservoir for platinum at DNA and may act as intermediates of platinum compounds and transform them into Pt-DNA adducts [8][9][10][11][12]. At the same time, platinum drugs could be inactivated in the reactions with cysteine-rich proteins, like glutathione (GSH), or metallothionine (MT) [12].…”

Copper chaperone Atox1 interacts with the metal-binding domain of Wilson's disease protein in cisplatin detoxification

“…Most of the platinum in cisplatin-treated cells was found to be associated with biopolymers [27] or glutathione [28]. The reaction with glutathione was proposed to be one of the major routes of cisplatin detoxification in the cells [28,29]. Even in the cells overexpressing ATP7B, its abundance is very low compared with glutathione, which is present at millimolar concentrations, or even compared with the potential protein acceptors of cisplatin such as metallothionein [28] and thioredoxin [30].…”

EPR and electrochemistry of [NH4]trans-[RuCl4(DMSO)(L)] complexes (L = DMSO, py ). X-ray molecular structure of [pyH][RuCl4(DMSO)(py)]

“…This seems to be transported to the cancer cell where the low Cl -concentration causes a subsequent hydration to produce higher aqua complexes that can then bind to DNA 2 . This aqua complex is more labile than the corresponding chloro complexes and are therefore considered to be the active species for the antitumor activity [5][6][7][8][9][10][11][12][13][14][15][16] . This information reveals that the development of these complexes as an alternative to platinum metal inhibitors is of special interest and ruthenium compounds have been studied extensively for this purpose.…”