New Findings in the Signaling Pathways of cis and trans Platinum Iodido Complexes’ Interaction with DNA of Cancer Cells

Abstract

We have selected a series of aliphatic amine platinum compounds bearing chloride and/or iodide as the leaving groups. The complexes’ cytotoxicity and interaction with DNA indicated differences in the reactivity. Now, we are reporting on the analysis of their molecular mechanism of action on gastric cancer cells. Our data reveals differences between them. Chlorido drugs showed similar behavior to cisplatin; they both required p53 to induce apoptosis but only cis-ipa showed DNA damage requirement for apoptosis induction. On the contrary, cis and trans iodido induced cell death independent of p53 activity, and they induced cell death through Bid activation, so their toxicity could be enhanced in a combined treatment with novel Bcl-2 protein family inhibitors. We also report the structural features of the DNA adduct for one of the complexes by X-ray diffraction. These findings represent a step forward in the search for new platinum-derived agents more specific and effective in the treatment of cancer.

Rhodium(III) Dihalido Complexes: The Effect of Ligand Substitution and Halido Coordination on Increasing Cancer Cell Potency

“…In particular, the N-(3bromophenyl)picolinamide substituted Ru(III) diiodido complex exhibited nanomolar potency against several cancer cell lines. Overall, the diiodido complexes were ∼13× more cytotoxic than the analogous dichlorido complexes, highlighting potentially different modes of action, similar to the Pt(II) work reported by Quiroga et al 8 Since we have already reported the potential of using picolinamide ligands to increase cytotoxicity of metal complexes, 27−29 we provide further insight into the biological cytotoxicity and the stability of the cis and trans dihalido complexes, by reporting eight new N-((3-halidophenyl)picolinamide)rhodium(III) dihalido complexes, [RhX 2 (L)-(LH)], where X = chlorido (1−4) or iodido (5−8). The complexes are fully characterized, and we report seven new crystal structures.…”

“…In particular, the N -(3-bromophenyl)­picolinamide substituted Ru­(III) diiodido complex exhibited nanomolar potency against several cancer cell lines. Overall, the diiodido complexes were ∼13× more cytotoxic than the analogous dichlorido complexes, highlighting potentially different modes of action, similar to the Pt­(II) work reported by Quiroga et al…”

“…Cisplatin, cis- [Pt­(NH 3 ) 2 Cl 2 ] (CDDP), and its platinum derivatives are still the most frequently used transition metal complexes in the treatment of various cancer types . However, the corresponding trans isomer, transplatin (t rans -[(NH 3 ) 2 Cl 2 Pt]), remains therapeutically inactive. , It has been suggested that the orientation of the cis chlorides is key for therapeutic activity, whereby CDDP forms ∼80% of intrastrand DNA cross-links, while transplatin forms monoadducts and interstrand DNA cross-links. − In 2019 Quiroga et al reported a series of aliphatic amine Pt­(II) complexes and highlighted the cis dichlorido complexes have similar modes of action to cisplatin, while the trans diiodido complexes exhibit different modes of action and activate the cytoplasmic protein BID, suggesting a pro-apoptotic cascade. , Generally, Pt-based therapeutics have poor cancer cell selectivity, which is associated with many adverse side-effects and has led chemotherapy research toward new non Pt-based alternatives such as Ru, Os, Rh, and Ir complexes, − in an attempt to overcome some of these selectivity issues. In particular, organometallic complexes have been prominent, with many compounds exhibiting high potency toward cancerous cells, while remaining nontoxic toward normal cell types, allowing for a more targeted therapy and reduction in patient side effects …”

“…4−7 In 2019 Quiroga et al reported a series of aliphatic amine Pt(II) complexes and highlighted the cis dichlorido complexes have similar modes of action to cisplatin, while the trans diiodido complexes exhibit different modes of action and activate the cytoplasmic protein BID, suggesting a pro-apoptotic cascade. 8,9 Generally, Pt-based therapeutics have poor cancer cell selectivity, which is associated with many adverse side-effects and has led chemotherapy research toward new non Pt-based alternatives such as Ru, Os, Rh, and Ir complexes, 10−12 in an attempt to overcome some of these selectivity issues. In particular, organometallic complexes have been prominent, with many compounds exhibiting high potency toward cancerous cells, while remaining nontoxic toward normal cell types, allowing for a more targeted therapy and reduction in patient side effects.…”

Parameter control and property analysis in the preparation of platinum iodide nanocolloids through the electrical spark discharge method

“…5 In physics, platinum is employed to produce organic lightemitting diodes. 6 Platinum is broadly applied in medicine, 7,8 including various cancer and drug treatments, [9][10][11] with spectacular results. Iodine is a nonmetallic chemical element and a nonarticial stable halogen.…”