New approach for the preparation of efficient DNA cleaving agents: ditopic copper-platinum complexes based on 3-Clip-Phen and cisplatin.
The design and synthesis of new heterodinuclear DNA-targeting agents are described. The abilities of cisplatin and Cu(3-Clip-Phen) [Cu(1-(1,10-phenanthrolin-3-yloxy)-3-(1,10-phenanthrolin-8-yloxy)propan-2-amine)Cl2], an artificial DNA-cleaving agent, have been combined through their "covalent coupling". This strategy has led to bifunctional complexes that are able to cleave the DNA in a double-stranded fashion in contrast to Cu(3-Clip-Phen) alone and have promising cytotoxicities compared to cisplatin in several cell lines.
Hoog
Paul de
Pd
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Post Office Box 9502, 2300 RA Leiden, The Netherlands.
Boldron
Christophe
C
Gamez
Patrick
P
Sliedregt-Bol
Karen
K
Roland
Isabelle
I
Pitié
Marguerite
M
Kiss
Robert
R
Meunier
Bernard
B
Reedijk
Jan
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D053837:DNA Cleavage; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C531042:dichloro(1-(1,10-phenanthrolin-3-yloxy)-3-(1,10-phenanthrolin-8-yloxy)propane-2-amine)copper(II); D002945:Cisplatin