title: Tuning the activity of platinum(IV) anticancer complexes through asymmetric acylation.
abstract: Platinum(II) anticancer drug cisplatin is one of the most important chemotherapeutic agents in clinical use but is limited by its high toxicity and severe side effects. Platinum(IV) anticancer prodrugs can overcome these limitations by resisting premature aquation and binding to essential plasma proteins. Structure-activity relationship studies revealed a link between the efficacy of platinum(IV) complexes with the nature of their axial ligands, which can be modified to enhance the properties of the prodrug. The existing paradigm of employing platinum(IV) complexes with symmetrical axial carboxylate ligands does not fully exploit their vast potential. A new approach was conceived to control properties of platinum(IV) prodrugs using contrasting axial ligands via sequential acylation. We report a novel class of asymmetric platinum(IV) carboxylates based on the cisplatin template containing both hydrophilic and lipophilic ligands on the same scaffold designed to improve their aqueous properties and enhance their efficacy against cancer cells in vitro.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543 Singapore.
authors.forename: Chee Fei
authors.initials: CF
authors.lastname: Chin
authors.forename: Quan
authors.initials: Q
authors.lastname: Tian
authors.forename: Magdiel Inggrid
authors.initials: MI
authors.lastname: Setyawati
authors.forename: Wanru
authors.initials: W
authors.lastname: Fang
authors.forename: Emelyn Sue Qing
authors.initials: ES
authors.lastname: Tan
authors.forename: David Tai
authors.initials: DT
authors.lastname: Leong
authors.forename: Wee Han
authors.initials: WH
authors.lastname: Ang
mesh_terms: D000215:Acylation; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D010984:Platinum