Abstract
We prepared a Pt(iv)-prodrug, which under cancer specific conditions (elevated concentration of reactive oxygen species, ROS) releases a DNA-binding drug oxaliplatin as well as ROS-amplifying drugs p-quinone methide and N-alkylferrocenium. Due to the concerted action of these components, an excellent anticancer effect was achieved: IC50 = 0.4 ± 0.1 μM for human ovarian carcinoma A2780 cells. Importantly, the prodrug was found to be 45-fold less toxic to normal cells (HDFa).
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Cell Cycle / drug effects
-
Cell Line
-
Cell Proliferation / drug effects
-
Dose-Response Relationship, Drug
-
Drug Screening Assays, Antitumor
-
Female
-
Humans
-
Molecular Conformation
-
Organoplatinum Compounds / chemical synthesis
-
Organoplatinum Compounds / chemistry
-
Organoplatinum Compounds / pharmacology*
-
Ovarian Neoplasms / drug therapy*
-
Ovarian Neoplasms / metabolism
-
Ovarian Neoplasms / pathology
-
Oxaliplatin
-
Prodrugs / chemical synthesis
-
Prodrugs / chemistry
-
Prodrugs / pharmacology*
-
Reactive Oxygen Species / metabolism
-
Structure-Activity Relationship
Substances
-
Antineoplastic Agents
-
Organoplatinum Compounds
-
Prodrugs
-
Reactive Oxygen Species
-
Oxaliplatin