Enhancement of aqueous solubility and stability employing a trans acetate axis in trans planar amine platinum compounds while maintaining the biological profile.
A general approach to solubilization and possible in vivo activation of the transplatinum geometry is presented. The synthesis and characterization of new water-soluble cytotoxic transplatinum compounds are described. Use of acetate ligands (and carboxylate ligands in general) in trans-[Pt(OAc)(2)(L)(L')] results in significantly enhanced aqueous solubility and chemical stability in comparison to the parent dichlorides. The new compounds are the first cytotoxic transplatinum compounds containing an N(2)O(2) donor set, similar to carboplatin and oxaliplatin.
Ma
Erin S F
ES
Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284-2006, USA.
Bates
W Douglas
WD
Edmunds
Armistead
A
Kelland
Lloyd R
LR
Fojo
Tito
T
Farrell
Nicholas
N
D000085:Acetates / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006868:Hydrolysis; D009944:Organoplatinum Compounds / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water
D000085:Acetates; D000588:Amines; D000970:Antineoplastic Agents; D002614:Chelating Agents; D009944:Organoplatinum Compounds; D014867:Water