Using phosphine ligands with a biological role to modulate reactivity in novel platinum complexes

Abstract

Three platinum complexes with cis and trans configuration cis-[Pt(TCEP)2Cl2], cis-[Pt(tmTCEP)2Cl2] and trans-[Pt(TCEP)2Cl2], where TCEP is tris(2-carboxyethyl)phosphine, have been synthesized and fully characterized by usual techniques including single-crystal X-ray diffraction for trans-[Pt(TCEP)2Cl2] and cis-[Pt(tmTCEP)2Cl2]. Here, we also report on an esterification process of TCEP, which takes place in the presence of alcohols, leading to a platinum complex coordinated to an ester tmTCEP (2-methoxycarbonylethyl phosphine) ligand. The stability in solution of the three compounds and their interaction with biological models such as DNA (pBR322 and calf thymus DNA) and proteins (lysozyme and RNase) have also been studied.

Thiosemicarbazone Derivatives as Inhibitors of Amyloid-β Aggregation: Effect of Metal Coordination

“…In a first instance, the potentially amyloidogenic protein lysozyme (hereditary lysozyme amyloidosis) was used to investigate the interaction of the metal complexes with a “model protein” that is broadly employed for interaction studies with metallodrugs. , The kinetic constants corresponding to the interaction of the different compounds with lysozyme were obtained considering a pseudo-first-order reaction (see Experimental Section for details and Figure and Figure S3). The values achieved (at λ = 433 nm) were compared to that of the reference compound cisplatin; k obs = 1.98 × 10 –4 s –1 was determined for cisplatin under the same experimental conditions (to those used for 1 – 3 ), which matches reported values …”

“…The values achieved (at λ = 433 nm) were compared to that of the reference compound cisplatin; k obs = 1.98 × 10 −4 s −1 was determined for cisplatin under the same experimental conditions (to those used for 1−3), which matches reported values. 41 For 1−3, the kinetic data were determined from the spectra shown in Figure 3 and Figure S3. The k obs values for 1 and 2 are in the range (0.4−1) × 10 −4 s −1 (Table 1).…”

New Platinum(II) Triazole Thiosemicarbazone Complexes: Analysis of Their Reactivity and Potential Antitumoral Action

“…Cisplatin binds covalently to DNA and to pBR322, producing ad elay in its closed circular form (cc) and slowing down the open circular form (oc) because of its unwinding. [21][22][23] Complexes 1 and 3 werea ssayed at different concentrations after 24 h( Figure 5) and the cisplatin experiment was also assayed as ac ontrol experiment.T he electrophoresis results showedt he expected resultsf or cisplatin. Complex 1 did not seem to alter the electrophoretic mobility of the plasmid The results observedi nt he experiment for complex 3 (lines 3t o6 )d on ot show relevant covalent behavior similar to that of cisplatin ( Figure 5, lines 11 to 13).…”

Pentafluorophenyl Platinum(II) Complexes of PTA and Its N-Allyl and N-Benzyl Derivatives: Synthesis, Characterization and Biological Activity

“…Platinum(II) complexes with trans geometry have proved to be interesting candidates to replace the commonly used cisplatin in view of its known adverse effects (mainly its toxicity) and to overcome acquired resistance (due to DME, drug-metabolizing enzymes or genetic variation) [74,75,76,77]. Trans-bisphosphino Pt(II) complexes have shown antiproliferative activity, being able to generate reactive oxygen species, targeting both mitochondria and genomic DNA [78], but also showed affinity toward protein models comparable or higher than cisplatin [79].…”