Computational study on the endocrine-disrupting metabolic activation of Benzophenone-3 catalyzed by cytochrome P450 1A1: A QM/MM approach.
Chemosphere
; 358: 142238, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38705413
ABSTRACT
Predicting the metabolic activation mechanism and potential hazardous metabolites of environmental endocrine-disruptors is a challenging and significant task in risk assessment. Here the metabolic activation mechanism of benzophenone-3 catalyzed by P450 1A1 was investigated by using Molecular Dynamics, Quantum Mechanics/Molecular Mechanics and Density Functional Theory approaches. Two elementary reactions involved in the metabolic activation of BP-3 with P450 1A1 electrophilic addition and hydrogen abstraction reactions were both discussed. Further conversion reactions of epoxidation products, ketone products and the formaldehyde formation reaction were investigated in the non-enzymatic environment based on previous experimental reports. Binding affinities analysis of benzophenone-3 and its metabolites to sex hormone binding globulin indirectly demonstrates that they all exhibit endocrine-disrupting property. Toxic analysis shows that the eco-toxicity and bioaccumulation values of the benzophenone-3 metabolites are much lower than those of benzophenone-3. However, the metabolites are found to have skin-sensitization effects. The present study provides a deep insight into the biotransformation process of benzophenone-3 catalyzed by P450 1A1 and alerts us to pay attention to the adverse effects of benzophenone-3 and its metabolites in human livers.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzofenonas
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Citocromo P-450 CYP1A1
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Disruptores Endócrinos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article