Biological activity of enantiomeric complexes [PtCl(2)L (2)] (L (2) is aromatic bisphosphanes and aromatic diamines).

Abstract

Enantiomeric complexes of formula [PtCl(2)L(2)] [L(2) is (R)-(+)-BINAP and (S)-(-)-BINAP, where BINAP is 2,2'-bis(diphenylphosphane)-1,1'-binaphthyl, and (R)-(+)-DABN and (S)-(-)-DABN, where DABN is 1,1'-binaphthyl-2,2'-diamine], were tested for their cytotoxic activity against three cancer cell lines and for their ability to bind to the human telomeric sequence folded in the G-quadruplex structure. Similar experiments were carried out on prototypal complexes cisplatin and cis-[PtCl(2)(PPh(3))(2)] for comparison. Platinum complexes containing phosphanes proved less cytotoxic to cancer cell lines and less likely to interact with the nucleobases of the G-quadruplex than those containing amines; in both cases the S-(-) isomer was more active than the R-(+) counterpart. More specifically, whereas all the platinum complexes were able to platinate the G-quadruplex structure from the human telomeric repeat, the extent and sites of platination depended on the nature of the ligands. Complexes containing (bulky) phosphanes interacted only with the adenines of the loops, whereas those containing the less sterically demanding amines interacted with adenines and some guanines of the G-quartet.

• Authors: Sophie Bombard, Marzia Bruna Gariboldi, Elena Monti, Elisabetta Gabano, Luca Gaviglio, Mauro Ravera, Domenico Osella
• Journal: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry (J Biol Inorg Chem) Vol. 15 Issue 6 Pg. 841-50 (Aug 2010) ISSN: 1432-1327 [Electronic] Germany
• PMID: 20333420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Diamines
• Organoplatinum Compounds
• Phosphines
• DNA
• phosphine

Topics

• Antineoplastic Agents (chemistry, metabolism, pharmacology)
• Binding Sites
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA (chemistry, metabolism)
• Diamines (chemistry)
• G-Quadruplexes
• Humans
• Kinetics
• Organoplatinum Compounds (chemistry, metabolism, pharmacology)
• Phosphines (chemistry)
• Stereoisomerism