Quinoxaline-2-carboxamide as a carrier ligand in two new platinum(II) compounds: Synthesis, crystal structure, cytotoxic activity and DNA interaction.
The search for platinum compounds structurally different from cisplatin has led to two new platinum(II) compounds containing quinoxaline-2-carboxamide as a carrier ligand, i.e. cis-[Pt(qnxca)(MeCN)Cl2] (1) and the [Pt(qnxca-H)(dmso)Cl] (2). Both compounds have been synthesized and characterized using different spectroscopic methods. In addition, single-crystal structures have been determined by X-Ray diffraction for both compounds. In each case a square planar Pt(II) is present; in (1) the qnxca is monodentate and neutral, whereas in (2) the ligand has lost a hydrogen, to form the anionic chelating ligand abbreviated as qnxca-H. The biological activity of both compounds has been investigated in a panel of seven human tumour cells, displaying poor cytotoxic activity, compared to cisplatin. The interaction of the new compounds with 1 or 2 equiv. of 9-ethylguanine has been studied using (1)H NMR, (195)Pt NMR and ESI-MS spectroscopy, finding poor reactivity of 1 towards the model base, forming only the monosubstituted adduct. Surprisingly, compound 2, which is more sterically crowded, interacts more efficiently with the 9-EtG, forming a bifunctional adduct with two 9-EtG with substitution of the dmso and the chloride ligand. Unwinding studies of pUC19 plasmid DNA by compound 1 show similar unwinding properties to cisplatin.
Marqués-Gallego
Patricia
P
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA, Leiden, The Netherlands. reedijk@chem.leidenuniv.nl.
Gamiz-Gonzalez
M Amparo
MA
Fortea-Pérez
Francisco R
FR
Lutz
Martin
M
Spek
Anthony L
AL
Pevec
Andrej
A
Kozlevčar
Bojan
B
Reedijk
Jan
J
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010957:Plasmids; D011810:Quinoxalines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D011810:Quinoxalines; C000599034:quinoxaline-2-carboxamide; D004247:DNA; D002945:Cisplatin