Semicarbazide is a widespread food contaminant that is produced by multiple pathways. However, the toxicity of semicarbazide to human health remains unclear. Using a highly accurate and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry method, we identified and quantitated in this study for the first time the DNA and RNA adduct of semicarbazide in DNA/RNA isolated from the internal organs of semicarbazide-exposed rats. The analysis revealed a dose-dependent formation of the adducts in the internal organs of the semicarbazide-dosed rats and with the highest adduct levels identified in the stomach and small intestine. Furthermore, results showed significantly higher levels of the RNA adduct (4.1-7.0 times) than that of the DNA adducts. By analyzing DNA/RNA samples isolated from rat organs in semicarbazide-dosed rats at different time points postdosing, the adduct stability in vivo was also investigated. These findings suggest that semicarbazide could have exerted its toxicity by affecting both the transcription and translation processes of the cell.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/acs.chemrestox.6b00232 | DOI Listing |
Luminescence
November 2023
Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia.
The increased resistance to antibiotics has compelled researchers to devise novel active compounds targeting multidrug-resistant pathogenic microorganisms. A series of thiosemicarbazone derivatives was synthesized by reacting thiosemicarbazide with 2-aryl-4-formylthiazole, 2-aryl-5-formyl-4-methylthiazole, and/or 5-acetyl-2-aryl-4-methylthiazole compounds. These thiosemicarbazone-based thiazole adducts were evaluated for their inhibitory activities against tuberculosis H37Ra and Bovis BCG mycobacteria.
View Article and Find Full Text PDFEur J Med Chem
June 2023
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Química Medicinal, Buenos Aires, C1113AAD, Argentina; CONICET-Universidad de Buenos Aires, Instituto de la Química y el Metabolismo del Fármaco (IQUIMEFA), Buenos Aires, 1113, Argentina. Electronic address:
Based on the activity of 23 TSCs on CZ taken from the literature, we have developed a QSAR model for predicting the activity of TSCs. New TSCs were designed and then tested against CZP, resulting in inhibitors with IC values in the nanomolar range. The modelling of the corresponding TSC-CZ complexes by molecular docking and QM/QM ONIOM refinement indicates a binding mode compatible with what was expected for active TSCs, according to a geometry-based theoretical model previously developed by our research group.
View Article and Find Full Text PDFInorg Chem
January 2023
Departamento de Química Inorgánica, Facultade de Química, Instituto de Investigación Sanitaria Galicia Sur, Universidade de Vigo, Campus Universitario, E-36310 Vigo, Galicia, Spain.
Nine potentially S,N,N-tridentate thiosemicarbazones (HL) derived from pyridine-2-carbaldehyde or 1-(2-pyridyl)ethanone have been prepared and fully characterized. The X-ray crystal structures of six of them and two hydrochlorides were determined and analyzed. The reaction of the [ReX(CHCN)(CO)]/[ReX(CO)] (X = Cl and Br) precursors with these ligands yielded different kinds of compounds: the adducts [ReX(HL)(CO)], in which the ligands were S,N-bidentate; the trinuclear species and the thiosemicarbazonate compounds [Re(L)(CO)], where the ligand is S,N,N-tridentate.
View Article and Find Full Text PDFJ Phys Chem Lett
September 2021
Department of Chemistry, East Carolina University, Greenville, North Carolina 27858, United States.
Ribonucleotide reductase (RNR), which supplies the building blocks for DNA biosynthesis and its repair, has been linked to human diseases and is emerging as a therapeutic target. Here, we present a mechanistic investigation of triapine (3AP), a clinically relevant small molecule that inhibits the tyrosyl radical within the RNR β subunit. Solvent kinetic isotope effects reveal that proton transfer is not rate-limiting for inhibition of Y122· of RNR β by the pertinent 3AP-Fe(II) adduct.
View Article and Find Full Text PDFJ Med Chem
November 2020
Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 42, Vienna 1090, Austria.
COTI-2 is a novel anticancer thiosemicarbazone in phase I clinical trial. However, the effects of metal complexation (a main characteristic of thiosemicarbazones) and acquired resistance mechanisms are widely unknown. Therefore, in this study, the copper and iron complexes of COTI-2 were synthesized and evaluated for their anticancer activity and impact on drug resistance in comparison to metal-free thiosemicarbazones.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!