Stability, protein binding and thiol interaction studies on [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt.
Cobalt-alkyne complexes are a new class of potent cytotoxic drugs. The lead compound [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt (Co-ASS) showed high effects on several human cancer cell lines. In order to evaluate further the in-vitro properties and reactivity of this substance we performed stability and protein binding studies and investigated the interaction of this complex with 1,2-ethanedithiol, L-cysteine and glutathione. UV-Vis, HPLC and AAS studies showed that the compound was sufficiently stable under in-vitro conditions. Binding to human serum albumin increased from approximately 25% at the beginning to over 50% after 48 h of incubation as determined by ethanol preciptation and size exclusion chromatography. The interaction with thiols resulted in disulfide bond formation of the thiols.
Ott
Ingo
I
Institute of Pharmacy, Free University of Berlin, Koenigin-Luise-Str. 2 + 4, 14195 Berlin.
Gust
Ronald
R
D002850:Chromatography, Gel; D003035:Cobalt / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000737:chemistry*
C505098:(2-acetoxy-(2-propynyl)benzoate)exacarbonyldicobalt; D009942:Organometallic Compounds; D011506:Proteins; D013438:Sulfhydryl Compounds; D003035:Cobalt