Combinatorial discovery of new asymmetric cis platinum anticancer complexes is made possible with solid-phase synthetic methods.
To efficiently access asymmetric cis platinum (II) complexes for biological evaluation, a new solid-phase synthesis was designed. This synthesis was used for the preparation of a small library of platinum compounds. Several compounds from this library revealed promising activity during a cytotoxicity screen. Two active compounds were, therefore, synthesised on a larger scale and tested more extensively against a larger panel of cell-lines, confirming their high potential as antitumour compounds. The work presented illustrates how a combination of a new methodology and established techniques can speed up the search for platinum complexes with improved cytotoxic profiles compared to cisplatin.
van Zutphen
Steven
S
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Stone
Elizabeth A
EA
van Rijt
Sabine
S
Robillard
Marc S
MS
van der Marel
Gijs A
GA
Overkleeft
Herman S
HS
den Dulk
Hans
H
Brouwer
Jaap
J
Reedijk
Jan
J
D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017671:Platinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017671:Platinum Compounds; D002945:Cisplatin