673-68-7Relevant academic research and scientific papers
Oxidative Release of Copper from Pharmacologic Copper Bis(thiosemicarbazonato) Compounds
Sirois, John J.,Padgitt-Cobb, Lillian,Gallegos, Marissa A.,Beckman, Joseph S.,Beaudry, Christopher M.,Hurst, James K.
, p. 8923 - 8932 (2018/08/17)
Intracellular delivery of therapeutic or analytic copper from copper bis-thiosemicabazonato complexes is generally described in terms of mechanisms involving one-electron reduction to the Cu(I) analogue by endogenous reductants, thereby rendering the metal ion labile and less strongly coordinating to the bis-thiosemicarbazone (btsc) ligand. However, electrochemical and spectroscopic studies described herein indicate that one-electron oxidation of CuII(btsc) and ZnIIATSM (btsc = diacetyl-bis(4-methylthiosemicarbazonato)) complexes occurs within the range of physiological oxidants, leading to the likelihood that unrecognized oxidative pathways for copper release also exist. Oxidations of CuII(btsc) by H2O2 catalyzed by either myeloperoxidase or horseradish peroxidase, by HOCl and taurine chloramine (which are chlorinating agents generated primarily in activated neutrophils from MPO-catalyzed reactions), and by peroxynitrite species (ONOOH, ONOOCO2-) that can form under certain conditions of oxidative stress are demonstrated. Unlike reduction, the oxidative reactions proceed by irreversible ligand oxidation, culminating in release of Cu(II). 2-Pyridylazoresorcinol complexation was used to demonstrate that Cu(II) release by reaction with peroxynitrite species involved rate-limiting homolysis of the peroxy O-O bond to generate secondary oxidizing radicals (NO2?, ?OH, and CO3?-). Because the potentials for CuII(btsc) oxidation and reduction are ligand-dependent, varying by as much as 200 mV, it is clearly advantageous in designing therapeutic methodologies for specific treatments to identify the operative Cu-release pathway.
Copper complexes with dissymmetrically substituted bis(thiosemicarbazone) ligands as a basis for PET radiopharmaceuticals: Control of redox potential and lipophilicity
Brown, Oliver C.,Bagu?a Torres, Julia,Holt, Katherine B.,Blower, Philip J.,Went, Michael J.
, p. 14612 - 14630 (2017/11/06)
Copper(ii) bis(thiosemicarbazone) derivatives have been used extensively in positron emission tomography (PET) to image hypoxia and blood flow and to radiolabel cells for cell tracking. These applications depend on control of redox potentials and lipophilicity of the bis(thiosemicarbazone) complexes, which can be adjusted by altering peripheral ligand substituents. This paper reports the synthesis of a library of new dissymmetrically substituted bis(thiosemicarbazone) ligands by controlling the condensation reactions between dicarbonyl compounds and 4-substituted-3-thiosemicarbazides or using acetal protection. Copper complexes of the new ligands have been prepared by reaction with copper acetate or via transmetallation of the corresponding zinc complexes, which are convenient precursors for the rapid synthesis of radio-copper complexes. Well-defined structure-activity relationships linking ligand alkylation patterns with redox potential and lipophilicity of the complexes are reported.
Identification of differential anti-neoplastic activity of copper bis(thiosemicarbazones) that is mediated by intracellular reactive oxygen species generation and lysosomal membrane permeabilization
Stefani, Christian,Al-Eisawi, Zaynab,Jansson, Patric J.,Kalinowski, Danuta S.,Richardson, Des R.
, p. 20 - 37 (2015/09/07)
Bis(thiosemicarbazones) and their copper (Cu) complexes possess unique anti-neoplastic properties. However, their mechanism of action remains unclear. We examined the structure-activity relationships of twelve bis(thiosemicarbazones) to elucidate factors
SYNTHESIS OF DERIVATIVES OF 1,2,4-TRIAZIN-3-THIONE AND 5-AMINO-2-ACYL-2,3-DIHYDRO-1,3,4-THIADIAZOLIUM SALTS FROM 1,2-DICARBONYL COMPOUNDS AND 4-SUBSTITUTED THIOSEMICARBAZIDES
Zelenin, K. N.,Kuznetsova, O. B.,Alekseev, V. V.
, p. 1211 - 1218 (2007/10/02)
The reactions of methyl- and phenylglyoxal with 2,4-disubstituted thiosemicarbazides and of diacetyl with 4-monosubstituted thiosemicarbazides gave monothiosemicarbazones which were converted in trifluoroacetic acid into previously unknown 5-amino-2-acyl-
