Metabolism of carbosulfan II. Human interindividual variability in its in vitro hepatic biotransformation and the identification of the cytochrome P450 isoforms involved was written by Abass, Khaled;Reponen, Petri;Mattila, Sampo;Pelkonen, Olavi. And the article was included in Chemico-Biological Interactions in 2010.Application of 1563-38-8 This article mentions the following:
This study aims to characterize interindividual variability and individual CYP enzymes involved in the in vitro metabolism of the carbamate insecticide carbosulfan. Microsomes from ten human livers (HLM) were used to characterize the interindividual variability in carbosulfan activation. Altogether eight phase I metabolites were analyzed by LC-MS. The primary metabolic pathways were detoxification by the initial oxidation of sulfur to carbosulfan sulfinamide ( sulfur oxidation pathway’) and activation via cleavage of the nitrogen sulfur bond (N-S) to give carbofuran and dibutylamine ( carbofuran pathway’). Differences between maximum and min. carbosulfan activation values with HLM indicated nearly 5.9-, 7.0, and 6.6-fold variability in the k m, V max and CLint values, resp. CYP3A5 and CYP2B6 had the greatest efficiency to form carbosulfan sulfinamide, while CYP3A4 and CYP3A5 were the most efficient in the generation of the carbofuran metabolic pathway. Based on average abundances of CYP enzymes in human liver, CYP3A4 contributed to 98% of carbosulfan activation, while CYP3A4 and CYP2B6 contributed 57 and 37% to detoxification, resp. Significant correlations between carbosulfan activation and CYP marker activities were seen with CYP3A4 (omeprazole sulfoxidation), CYP2C19 (omeprazole 5-hydroxylation) and CYP3A4 (midazolam 1′-hydroxylation), displaying r 2 = 0.96, 0.87 and 0.82, resp. Activation and detoxification pathways were inhibited by ketoconazole, a specific CYP3A4 inhibitor, by 90-97% and 47-94%, resp. Carbosulfan inhibited relatively potently CYP3A4 and moderately CYP1A1/2 and CYP2C19 in pooled HLM. These results suggest that the carbosulfan activation pathway is more important than the detoxification pathway, and that carbosulfan activation is predominantly catalyzed in humans by CYP3A4. In the experiment, the researchers used many compounds, for example, 2,2-Dimethyl-2,3-dihydrobenzofuran-7-ol (cas: 1563-38-8Application of 1563-38-8).
2,2-Dimethyl-2,3-dihydrobenzofuran-7-ol (cas: 1563-38-8) belongs to benzofurans derivatives. Benzofurans are only weakly aromatic in nature and they are cleaved by many oxidative and reductive conditions. In nature, benzofurans have occupied an important role among the plant phenols & several pharmacologically active compounds.Application of 1563-38-8
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem