Relevance of the leaving group for antitumor activity of new platinum(II) compounds containing anthracene derivatives as a carrier ligand.
A new anticancer-active platinum(II) compound [Pt(A9pyp)(dmso)(cbdca)], containing the E-1-(9-anthryl)-3-(2-pyridyl)-2-propenone ligand (abbreviated as A9pyp) has been synthesized by the replacement of the anionic chloride ligands in cis-[Pt(A9pyp)(dmso)Cl(2)] by the dianionic chelating cyclobutanedicarboxylate ligand (abbreviated as cbdca). The in vitro relevance of the leaving group of these new platinum(II) compounds has been investigated. Measurements of the time-dependent intracellular accumulation of both compounds in human ovarian carcinoma cell lines show that the leaving group affects their cellular uptake. In addition, the leaving group also influences DNA platination, and, therefore, has an effect on the biological activity against a pair of human ovarian carcinoma cell lines, i.e. sensitive and resistant to cisplatin.
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Patricia
P
Marqués-Gallego
Simone
S
Contaldi
Hans
H
den Dulk
Magda
M
Monari
Jaap
J
Brouwer
Ulrich
U
Jaehde
Ganna V
GV
Kalayda
Jan
J
Reedijk
D000873:Anthracenes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D008024:Ligands; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism*
D000873:Anthracenes; D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; C034020:anthracene; D002945:Cisplatin