Indirect evidences of desulfurization of a thiosemicarbazonecopper(II) system in aqueous basic medium

Gómez-Saiz, Patricia; García–Tojal, Javier; Díez‐Gómez, Virginia; Gil‐García, Rubén; Pizarro, José L.; Arriortua, Marı́a I.; Rojo, Teófilo

doi:10.1016/j.inoche.2004.12.016

Cited by 29 publications

(24 citation statements)

References 30 publications

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“…Our observation that Cu 2+ potentiates the cytotoxic action of Dp44mT is consistent with the recent report showing a similar phenomenon [37]. Our observation that triapine is inactivated by Cu 2+ is in agreement with the report indicating an indirect evidence for desulfurization of a thiosemicarbazonecopper(II) complex in aqueous basic medium [38]. The reaction scheme for the triapine/Cu(II) complex undergoing base-catalyzed loss of sulfur and ultimately forming of a nitrile has been proposed [1].…”

Section: Discussionsupporting

confidence: 93%

Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes

Ishiguro

Lin

Penketh

et al. 2014

Biochemical Pharmacology

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Triapine, currently being evaluated as an antitumor agent in phase II clinical trials, and its terminally dimethylated derivative Dp44mT share the α-pyridyl thiosemicarbazone backbone that functions as ligands for transition metal ions. Yet, Dp44mT is approximately 100-fold more potent than triapine in cytotoxicity assays. The aims of this study were to elucidate the mechanisms underlying their potency disparity and to determine their kinetics of cell-kill in culture to aid in the formulation of their clinical dosing schedules. The addition of Cu2+ inactivated triapine in a 1:1 stoichiometric fashion, while it potentiated the cytotoxicity of Dp44mT. Clonogenic assays after finite-time drug-exposure revealed that triapine produced cell-kill in two phases, one completed within 20 min that caused limited cell-kill, and the other occurring after 16 h of exposure that produced extensive cell-kill. The ribonucleotide reductase inhibitor triapine at 0.4 µM caused immediate complete arrest of DNA synthesis, whereas Dp44mT at this concentration did not appreciably inhibit DNA synthesis. The inhibition of DNA synthesis by triapine was reversible upon its removal from the medium. Cell death after 16 h exposure to triapine paralleled the appearance of phospho-(γ)H2AX, a marker of DNA double-strand breaks induced by collapse of DNA replication forks after prolonged replication arrest. In contrast to triapine, Dp44mT produced robust cell-kill within 1 h in a concentration-dependent manner. The short-term action of both agents was prevented by thiols, indicative of the involvement of reactive oxygen species. The time dependency in the production of cell-kill by triapine should be considered in treatment regimens.

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Section: Discussionsupporting

confidence: 93%

Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes

Ishiguro

Lin

Penketh

et al. 2014

Biochemical Pharmacology

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“…The Cu(1) ion is five‐coordinate by two oxygen atoms belonging to two different carboxylate groups from two separated pht ligands [Cu(1)–O(3), 1.954(4); Cu(1)–O(4), 1.969(4) Å], two hydroxyl oxygen atoms with the bond lengths 1.897(4) Å [Cu(1)–O(5)] and 1.899(4) Å [Cu(1)–O(5A)], and one oxygen atom from a 4‐bpfp ligand [Cu(1)–O(6) = 2.704(4) Å] to complete a distorted tetragonal pyramidal arrangement. The Cu1–O Hydroxo bond lengths are within normal range,27–29 and the Cu1 ··· Cu1 separation distance (3.493 Å) is similar to other copper complexes containing a Cu II ‐bis(μ‐hydroxo) subunit 30. The other Cu II ion [Cu(2)] has a six‐coordinate, Jahn–Teller distorted octahedral arrangement and is coordinated by two oxygen atoms [O(2), O(2A)] from two pht ligands with distance of 1.933(5) Å [Cu(2)–O car ], two oxygen atoms from two coordination water molecules [the distances: Cu(2)–O(1W), Cu(2)–O(1WA), 2.582(3) Å], and two nitrogen atoms [N(1), N(1A)] from the pyridyl groups of two 4‐bpfp ligands [Cu(2)–N = 2.004(5) Å].…”

Section: Resultssupporting

confidence: 64%

Two Novel 3D Copper Phthalate Coordination Complexes Incorporating Isomeric Flexible Bis(pyridylformyl)piperazine Ligands

Huang

Wang

et al. 2012

Zeitschrift anorg allge chemie

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Two novel metal-organic coordination complexes [Cu(3bpfp)(pht)(H 2 O)]·2H 2 O (1) and [Cu 3 (4-bpfp)(pht) 2 (OH) 2 ]·2H 2 O (2) were hydrothermally synthesized by self-assembly of phthalic acid (H 2 pht), flexible bis(pyridylformyl)piperazine ligands [3-bpfp = bis(3pyridylformyl)piperazine, 4-bpfp = bis(4-pyridylformyl)piperazine], and copper chloride. Single crystal X-ray diffraction analysis revealed that the adjacent Cu II ions are connected by pht showing different coordination modes [a bis(monodentate) coordination mode for 1 and a monodentate-bidentate coordination mode for 2] to form 1D Cu-pht-Cu chains in 1 and 2D Cu-pht layers in 2. In compound 1, a twofold

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“…Recently, desulfurization of dithiocarbamatocadmium( II ) complexes in the presence of amines has been reported 16. In addition, there are indirect evidences of desulfurization of an analogous thiosemicarbazonecopper( II ) system in aqueous basic medium 17. However, the reactions described in these papers do not yield carbonitrile derivatives.…”

Section: Resultsmentioning

confidence: 99%

Unexpected Behaviour of Pyridine‐2‐carbaldehyde Thiosemicarbazonatocopper(II) Entities in Aqueous Basic Medium – Partial Transformation of Thioamide into Nitrile

et al. 2005

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Indirect evidences of desulfurization of a thiosemicarbazonecopper(II) system in aqueous basic medium

Cited by 29 publications

References 30 publications

Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes

Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes

Two Novel 3D Copper Phthalate Coordination Complexes Incorporating Isomeric Flexible Bis(pyridylformyl)piperazine Ligands

Unexpected Behaviour of Pyridine‐2‐carbaldehyde Thiosemicarbazonatocopper(II) Entities in Aqueous Basic Medium – Partial Transformation of Thioamide into Nitrile

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