Chemical, structural and biological studies of cis-[Pt(3-Acpy)(2)Cl(2)].
Recent developments in the field of platinum anticancer drugs have revealed that compounds containing derivates of pyridine may exhibit highly cytotoxic activity against a variety of tumor cells, with AMD473 (cis-PtCl(2)(NH(3))(2-methylpyridine)) as one of the most relevant examples. Following these advances, this paper describes the synthesis, characterization and X-ray structure of the square-planar compound cis-[Pt(3-Acpy)(2)Cl(2)] (1, Acpy stands for acetylpyridine), where the coordination of 3-acetylpyridine takes places through the pyridine nitrogen of the ligand. The structural arrangement of this compound is highly peculiar and it is the first example with two of these 3-acetylpyridine molecules in a cis disposition. In addition, the anticancer and antibacterial activities of this compound together with studies of DNA binding are also described in detail, with selective activity of compound 1 against A2780R cells. cis-[Pt(3-Acpy)(2)Cl(2)] apparently coordinates to the DNA double helix upon exchange of at least one of the Cl(-) ions with the media and shows very interesting bacteriolytic and bacteriostatic activity against Escherichia coli and Streptomyces, respectively.
Tian
Tian
T
Leiden Institute of Chemistry, Leiden University, The Netherlands.
Mutikainen
Ilpo
I
van Wezel
Gilles P
GP
Aliaga-Alcalde
Nuria
N
Reedijk
Jan
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000138:chemical synthesis / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D017186:Titrimetry; D044366:Transition Temperature
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D018736:DNA Adducts; D007202:Indicators and Reagents; D008024:Ligands; D009944:Organoplatinum Compounds; D011725:Pyridines; C544096:cis-3-acetylpyridinedichloridoplatinum; C010835:3-acetylpyridine; D004247:DNA; C427203:calf thymus DNA