Synthesis, characterization and biological activity of two new polymeric copper(II) complexes with alpha-ketoglutaric acid thiosemicarbazone.
In this paper we describe the synthesis of new copper complexes with alpha-ketoglutaric acid thiosemicarbazone. The crystal structures of the two compounds: [Cu(H(2)ct)Cl](n) [(Cu(H(2)ct)Cl)(2)] (1) and [Cu(Hct)](n).3nH(2)O (2) (H(3)ct=alpha-ketoglutaric acid thiosemicarbazone) have been determined by X-ray and spectroscopic methods. In 1 two independent copper atoms are present. Cu(1), in a nitrogen- and oxygen-bridged polymer, is a six-coordinated (4+2), Cu(2), five coordinated (4+1), is a chlorine-bridged dimer. In 2 the copper atom presents a penta-coordination, polymeric chains form layers and the -CH(2)CH(2)COO(-) groups bridge copper atoms. In 1 a monodentate and in 2 a syn-anti bidentate bridging carboxylate are present. The biological properties of 1 and 2 and also of the free ligand (H(3)ct) were tested in vitro and compared on Friend erythroleukemia cells (FLC) and on human leukemia cell lines K562 and U937. On the FLC cells the free ligand does not inhibit cell growth, but increases the DNA synthesis; complex 1 inhibits cell proliferation and increases the DNA synthesis; complex 2 inhibits cell growth, but induces a decrement of DNA synthesis and increases the reverse transcriptase activity. Regarding the human cell lines, both complexes show proliferation inhibition through an apoptosis mechanism on cell line U937, while they have no effects on the K562 line.
Belicchi Ferrari
Marisa
M
Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica, Chimica Fisica, Università di Parma, Centro di Studio per la Strutturistica Diffrattometrica del CNR, Parco Area delle Scienze 17/A, 43100, Parma, Italy. marisa.ferrari@unipr.it
Bisceglie
Franco
F
Gasparri Fava
Giovanna
G
Pelosi
Giorgio
G
Tarasconi
Pieralberto
P
Albertini
Roberto
R
Pinelli
Silvana
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003300:Copper / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D003300:Copper; D012194:RNA-Directed DNA Polymerase