Abstract:
:A dimeric copper complex of the unsubstituted pyridoxal thiosemicarbazone (H(2)L), [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O, previously tested on Friend murine cell lines has been recently resynthesized to evaluate its behavior on different murine and human leukemic cell lines and has been compared, in vitro and in vivo, with its monomeric counterpart [Cu(H(2)L)(OH(2))Cl]Cl. On TS/A murine adenocarcinoma cell line in vitro, both compounds significantly inhibit cell proliferation at micromolar concentrations, although the dimeric compound is more active. Despite this cytotoxicity they lack in vivo activity on TLX5 lymphoma. The unsubstituted dimeric [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O induces apoptosis on CEM and U937 human cell lines, with IC(50) concentrations of 1.2 x 10(-5) and 6.7 x 10(-6) M, respectively, but it is inactive on K562. Moreover, it alters significantly the cell cycle of U937 and CEM lines and decreases the telomerase activity of U937. To verify if other dimeric copper complexes show relevant biological activity new complexes with N-substituted pyridoxal thiosemicarbazones have been synthesized and characterized using spectroscopic techniques. Three of them, namely [Cu(Me(2)-HL)Cl](2).6H(2)O (Me(2)-H(2)L=pyridoxal N1,N1-dimethylthiosemicarbazone) (1), [Cu(MeMe-HL)Cl](2)Cl(2).4H(2)O (MeMe-HL=pyridoxal N1,N2-dimethylthiosemicarbazone) (2), [Cu(Et-H(2)L)Cl](2)Cl(2).2H(2)O (Et-H(2)L=pyridoxal N1-ethylthiosemicarbazone) (3), were also characterized by X-ray diffractometry. These complexes are dimeric and all three present a square pyramidal coordinative geometry with the ligand showing an SNO tridentate behavior. Their biological activities have been tested in vitro on U937, CEM and K562 cell lines to ascertain their effectiveness in comparison to the corresponding unsubstituted complex [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O. Compound 1 shows weak proliferation inhibition on all three cell lines, but it does not induce apoptosis and it does not inhibit telomerase activity, compound 2 is not effective at low concentration and is toxic at higher doses; compound 3 inhibits CEM cell growth better than complex 1 but it does not exert any other biological effect.
journal_name
J Inorg Biochemjournal_title
Journal of inorganic biochemistryauthors
Belicchi Ferrari M,Bisceglie F,Pelosi G,Tarasconi P,Albertini R,Dall'Aglio PP,Pinelli S,Bergamo A,Sava Gdoi
10.1016/j.jinorgbio.2003.09.011subject
Has Abstractpub_date
2004-02-01 00:00:00pages
301-12issue
2eissn
0162-0134issn
1873-3344pii
S0162013403003854journal_volume
98pub_type
杂志文章abstract::Novel bismuth(III) complexes 1-4 with the tridentate thiosemicarbazone ligand of 2N1S donor atoms [Hmtsc (L1); 2-acetylpyridine (4N-morpholyl thiosemicarbazone)], the pentadentate double-armed thiosemicarbazone ligand of 3N2S donor atoms [H2dmtsc (L3); 2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone)] and the ...
journal_title:Journal of inorganic biochemistry
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abstract::Cystine, selenocytsine, and several analogs were reduced by dithiothreitol (DTT), beta-mercaptoethanol (ME) and sodium borohydride (NaBH4). DTT was the most effective; DTT to cystine ratios from 10 to 80 were equally effective. With selenocysteine, however, absorption was considerably reduced at all ratios. Selenocyst...
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abstract::Zinc is an essential element for nutrition as well as for the proper development and function of brain cells, and its traces are present in a wide range of foods. It is a constituent of many enzyme systems and is an integral part of insulin and of the active site of intracellular enzymes. However, excessive accumulati...
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2010.12.005
更新日期:2011-04-01 00:00:00
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doi:10.1016/j.jinorgbio.2012.04.002
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abstract::Sulfur- and selenium-containing amino acids are of great biological importance, but their metal-binding properties with biologically-relevant metal ions are not well investigated. Stability constants of the methionine, selenomethionine, methylcysteine, and methylselenocysteine with Cu(II) and Fe(II) were determined by...
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abstract::Measurements of binding of certain divalent cations to yeast apoenolase were made using a pH-meter, chromatography, a divalent cation electrode, and ultrafiltration. The binding of the activating metal ions Mg2+ and Co2+ and the nonactivator Ca2+ were studied as functions of the presence or absence of substrate/produc...
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abstract::Seven ferrocenyl naphthalene diimide (FND) ligands were synthesized. Each had a higher affinity for tetraplex DNA than for either single- or double-stranded DNA. The FND binding affinities were >105M-1 in 0.10M AcOH-AcONa or AcOH-AcOK (pH5.5) containing 0.10M NaCl or KCl. The FNDs with the highest binding affinities f...
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abstract::The rational design of anticancer agents that acts in specific biological targets is one of the most effective strategies for developing chemotherapeutic agents. Aiming at obtaining new ruthenium (II) compounds with good cytotoxicity against tumor cells, a series of new complexes of general formula [RuCl(PPh3)(Hdpa)(N...
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journal_title:Journal of inorganic biochemistry
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abstract::Quaternary systems of copper(II) complexes with adenosine 5'-triphosphate, O-phospho L-serine and with equimolar or excessive amount of spermine have been investigated. The studies have been performed in aqueous solution. Types of complexes and the overall stability constants have been determined using the potentiomet...
journal_title:Journal of inorganic biochemistry
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