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The role of arylamine N-acetyltransferases in chronic degenerative diseases: Their possible function in the immune system.
Biochim Biophys Acta Mol Cell Res
September 2022
Faculty of Chemical Sciences, Autonomous University of San Luis Potosí, Mexico; Research Center for Health Sciences and Biomedicine, Autonomous University of San Luis Potosí, Mexico. Electronic address:
Since their discovery, arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2, respectively) have been associated with the metabolism of xenobiotics. NAT2 is the main factor in the therapeutic success of tuberculosis treatment due to its role in the biotransformation of isoniazid. However, researchers have started to investigate the possible participation of NAT1 and NAT2 (NATs) in carcinogenesis, although the mechanisms have not been elucidated fully.
View Article and Find Full Text PDFIsonicotinylation is a histone mark induced by the anti-tuberculosis first-line drug isoniazid.
Nat Commun
September 2021
Program for Cancer and Cell Biology, Department of Human Anatomy, Histology and Embryology, PKU International Cancer Institute, MOE Key Laboratory of Carcinogenesis and Translational Research and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, PR China.
Isoniazid (INH) is a first-line anti-tuberculosis drug used for nearly 70 years. However, the mechanism underlying the side effects of INH has remained elusive. Here, we report that INH and its metabolites induce a post-translational modification (PTM) of histones, lysine isonicotinylation (K), also called 4-picolinylation, in cells and mice.
View Article and Find Full Text PDFFunctional variability of rhesus macaque (Macaca mulatta) NAT2 gene for drug-metabolising arylamine N-acetyltransferase 2.
Biochem Pharmacol
June 2021
Democritus University of Thrace, Department of Molecular Biology and Genetics, Alexandroupolis, Greece. Electronic address:
Human NAT2 is a polymorphic pharmacogene encoding for N-acetyltransferase 2, a hepatic enzyme active towards arylamine and arylhydrazine drugs, including the anti-tubercular antibiotic isoniazid. The isoenzyme also modulates susceptibility to chemical carcinogenesis, particularly of the bladder. Human NAT2 represents an ideal model for anthropological investigations into the demographic adaptation of worldwide populations to their xenobiotic environment.
View Article and Find Full Text PDFNaphthoquinone-based Hydrazone Hybrids: Synthesis and Potent Activity Against Cancer Cell Lines.
Med Chem
December 2021
Graduate College of Health and Biological Sciences, Federal University of San Francisco Valley, Petrolina, PE, Brazil.
Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity.
Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β- lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity.
Relevance of mouse lung tumors to human risk assessment.
J Toxicol Environ Health B Crit Rev
July 2020
Exponent Inc ., Alexandria, VA, USA.
Mouse lung is a common site for chemical tumorigenicity, but the relevance to human risk remains debated. Long-term bioassays need to be assessed for appropriateness of the dose, neither exceeding Maximum Tolerated Dose (MTD) nor Kinetically based Maximum Dose (KMD). An example of the KMD issue is 1,3-dichloropropene (1,3-D), which only produced an increased incidence of lung tumors at a dose exceeding the KMD.
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