Platinum‐Sulfur Interactions Involved in Antitumor Drugs, Rescue Agents, and Biomolecules

Novel cis‐Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action

“…Before platinum drugs reach the DNA in the nucleus of tumor cells, they can interact with various sulfur-containing molecules because Pt(II) compounds show a strong thermodynamic preference for binding to sulfur donor ligands [ 43 ]. These interactions are generally thought to play a role in the mechanisms underlying the activity (inactivation) of Pt drugs [ 43 , 44 ]. The study of the interactions of platinum antitumor complexes with sulfur-containing compounds of biological importance may help elucidate other aspects of the action of the new Pt compounds.…”

Structural Characterization, DNA Interactions, and Cytotoxicity of New Transplatin Analogues Containing One Aliphatic and One Planar Heterocyclic Amine Ligand

“…Hence, before antitumor platinum(II) drugs reach DNA in the nucleus of tumor cells or even after they bind to DNA, they may interact with various compounds including sulfur-containing molecules . These interactions are generally believed to play a role in mechanisms underlying tumor resistance to platinum compounds, their inactivation and side effects. − In addition, a distinct difference between cisplatin and its clinically inefficient trans isomer is that transplatin is kinetically more reactive than cisplatin and more susceptible to deactivation. While cisplatin major adducts are intrastrand CLs between neighboring guanine residues, transplatin−DNA adducts are mainly interstrand CLs and a relatively large portion of adducts remains monofunctional (Figure and ref ).…”

Conformation and recognition of DNA modified by a new antitumor dinuclear PtII complex resistant to decomposition by sulfur nucleophiles

“…S3). Both clinical and preclinical studies have shown that cells with an elevated level of GSH (>10 mM) may be resistant to cisplatin and its analogues [54,55]. Thus, although it has been shown that reaction of 1 with GSH does not result in linker cleavage and loss of its dinuclear structure, further studies are warranted to determine whether deactivation by GSH is a strongly unfavorable determinant of cytotoxic effects of 1 .…”