DNA binding studies and cytotoxicity of a dinuclear PtII diazapyrenium-based metallo-supramolecular rectangular box.
The interaction with native DNA of a 2,7-diazapyrenium-based ligand 1 and its Pt(II) rectangular metallacycle 2 is explored through circular and linear dichroism and fluorescence spectroscopies. The metal-free ligand 1 binds through intercalation, with a binding constant of approximately 5×10(5) M(-1), whereas the metallacycle 2 binds and bends the DNA with a binding constant of 7×10(6) M(-1). PCR assays show that metallo-supramolecular box 2 interferes with DNA transactions in vitro whereas the intercalator 1 does not. The metallacycle is active against four human cancer cell lines, with IC(50) values ranging between 3.1 and 19.2 μM and shows similar levels of efficacy, but a different spectrum of activity, to cisplatin.
School of Chemistry, University of Birmingham, Edgbaston, Birmingham, UK.
Alessio
A
Terenzi
Cosimo
C
Ducani
Víctor
V
Blanco
Lenka
L
Zerzankova
Aron F
AF
Westendorf
Carlos
C
Peinador
José M
JM
Quintela
Patrick J
PJ
Bednarski
Giampaolo
G
Barone
Michael J
MJ
Hannon
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D002945:Cisplatin / Q000737:chemistry; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D008968:Molecular Conformation; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
C401953:2,7-diazapyrenium; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D010618:Phenanthrolines; D010984:Platinum; D002945:Cisplatin