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J Med Chem ; 67(8): 6081-6098, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38401050

ABSTRACT

In this work, we investigated the anticancer activity of several novel silver(I) 2,2'-bipyridine complexes containing either triphenylphosphane (PPh3) or 1,2-bis(diphenylphosphino)ethane (dppe) ligands. All compounds were characterized by diverse analytical methods including ESI-MS spectrometry; NMR, UV-vis, and FTIR spectroscopies; and elemental analysis. Moreover, several compounds were also studied by X-ray single-crystal diffraction. Subsequently, the compounds were investigated for their anticancer activity against drug-resistant and -sensitive cancer cells. Noteworthily, neither carboplatin and oxaliplatin resistance nor p53 deletion impacted on their anticancer efficacy. MES-OV cells displayed exceptional hypersensitivity to the dppe-containing drugs. This effect was not based on thioredoxin reductase inhibition, enhanced drug uptake, or apoptosis induction. In contrast, dppe silver drugs induced paraptosis, a novel recently described form of programmed cell death. Together with the good tumor specificity of this compound's class, this work suggests that dppe-containing silver complexes could be interesting drug candidates for the treatment of resistant ovarian cancer.


Subject(s)
2,2'-Dipyridyl , Antineoplastic Agents , Phosphines , Silver , Humans , Phosphines/chemistry , Phosphines/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Silver/chemistry , Silver/pharmacology , 2,2'-Dipyridyl/chemistry , 2,2'-Dipyridyl/pharmacology , Cell Line, Tumor , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Apoptosis/drug effects , Crystallography, X-Ray , Ligands , Cell Death/drug effects , Drug Screening Assays, Antitumor , Structure-Activity Relationship , Drug Resistance, Neoplasm/drug effects
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