Novel, quinone-thiosemicarbazone hybrid (QTSCHY) non-platinum antitumor agents: inhibition of DNA biosynthesis in P388 lymphocytic cells by coordinatively unsaturated copper(II) and iron(III) complexes of naphthoquinone thiosemicarbazones

Pyridine‐2‐carbaldehyde thiosemicarbazone and pyridine‐2‐carbaldehyde 4N‐methyl thiosemicarbazone ligands (HLI and HLImm respectively) undergo an oxidative cyclization when treated with bromate or iodate, leading to 2‐amino‐5‐pyridin‐2‐yl‐1,3,4‐oxadiazole and 2‐methylamino‐5‐pyridin‐2‐yl‐1,3,4‐oxadiazole (HLII and HLIImm). This reaction occurs either with free ligands or when coordinated to copper(II). Some of the starting ([{Cu(LImm)(NO3)}2] (3), intermediate Cu(LI)(IO3)·(H2O) (1), [{Cu(LI)I}2] (2), [{Cu(LImm)Br}2] (4), and final compounds [{Cu(HLII)(H2O)3}2](SO4)2 (5), [{Cu(HLIImm)(H2O)2(SO4)}2]·2H2O (6), (HLII) (7), [HLIImm]·3H2O (8) have been isolated and characterized by elemental analyses, IR, UV‐visible, NMR, and EPR spectroscopy. The structures of 2, 3, 4, 5, 6, and 8, solved by X‐ray diffraction methods, contain dinuclear entities with either square‐pyramidal (2, 3, 4) or octahedral (5, 6) copper(II) ions. Structural and spectroscopic results suggest that ligand‐to‐metal charge transfer occurs in these compounds. The EPR spectra at 120 K exhibit rhombic (1, 3, 4), isotropic (2), and axial (5, 6) signals. Magnetic measurements show antiferromagnetic couplings for 2, 4, 5, and 6. The susceptibility data were fitted by the Bleaney−Bowers equation for copper(II) dimers. The obtained J/k values are −20.20, −8.85, −2.75, and −2.78 K for 2, 4, 5, and 6, respectively. However, ferromagnetic intradimeric interactions are present in 3 (J/k = +9.90 K) together with antiferromagnetic interdimer coupling (z′J′/k = −1.70 K). Magneto‐structural studies show the influence of the non‐thiosemicarbazone coligand in the magnetic behaviour of these complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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“…Selected interatomic dimensions are given in Table 3. The crystal structure consists of cationic dimeric [{Cu(HL II )(H 2 O) 3 } 2 ]…”

Section: Crystal Structures Of the Oxadiazole Derivativesmentioning

confidence: 99%

New 1,3,4‐Oxadiazolecopper(II) Derivatives Obtained from Thiosemicarbazone Complexes

et al. 2003

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“…Indeed, an inhibition of the proliferation, particularly nuclear DNA synthesis, has been found to occur in spleen lymphoid cells (SLC) from copper-deficient rodents (Lukasiewicz & Prohaska 1983, Davis et al 1987, Kramer et al 1988. A more recent study (Padhye et al 1992) has revealed that naphtoquinone thiosemicarbazones--potent chelators of copper--efficiently inhibit DNA synthesis in P388 lymphocyte cells. Although thiosemicarbazones which strongly bind copper may have directly limited the availability of the metal for the cells in the latter case, in the former one the limitation of copper for SLC may have resulted from an accompanied deficiency of ceruloplasmin activity in the blood plasma (Kramer et al 1988) as this glycoprotein, synthesized in the liver, is thought to be a major copper donor to extrahepatic tissues (Cousins 1985).…”

Section: Copper and Cell Proliferationmentioning

confidence: 99%

Involvement of metallothionein and copper in cell proliferation

Włostowski

1993

Biometals

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Metallothionein is a low-molecular weight, cysteine-rich, metal-binding protein which has been implicated in the detoxification of toxic metals (cadmium, mercury), metabolism of zinc and copper, as well as in the scavenging of free radicals. Recent evidence suggests that the protein may also be involved in cell proliferation. Based on the experiments carried out so far, it is assumed that the fundamental role of metallothionein in cell proliferation may be to detoxify and/or transfer copper ions from the cytoplasm to the nucleus at the G1/S phase, which in turn participate in some way in nuclear DNA synthesis.

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“…There have been several reports on mononuclear complexes of tridentate thiosemicarbazones [2][3][4][5][6][7][8]. In most cases, salicylaldehyde is used as a starting material to give tridentate ligands.…”

Section: Introductionmentioning

confidence: 99%

Ligational behavior of new mononucleating SNOO thiosemicarbazone ligands towards 3d metal(II) ions: synthesis and spectroscopic studies

Baligar

Revankar

2007

Transition Met Chem

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A series of three new mononucleating thiosemicarbazone ligands possessing potential S, N, and O coordination sites have been prepared by the reaction of 2-formylphenoxy acetic acid with substituted thiosemicarbazides. Complexes of these ligands with Co II , Ni II , Cu II , and Zn II have prepared and characterized by physicochemical and spectroscopic methods. In all the complexes, the dibasic tetradentate nature of the ligand is evident.

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Novel, quinone-thiosemicarbazone hybrid (QTSCHY) non-platinum antitumor agents: inhibition of DNA biosynthesis in P388 lymphocytic cells by coordinatively unsaturated copper(II) and iron(III) complexes of naphthoquinone thiosemicarbazones

Cited by 21 publications

References 23 publications

New 1,3,4‐Oxadiazolecopper(II) Derivatives Obtained from Thiosemicarbazone Complexes

New 1,3,4‐Oxadiazolecopper(II) Derivatives Obtained from Thiosemicarbazone Complexes

Involvement of metallothionein and copper in cell proliferation

Ligational behavior of new mononucleating SNOO thiosemicarbazone ligands towards 3d metal(II) ions: synthesis and spectroscopic studies

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