Quantitative structure-activity relationships in a series of endogenous and synthetic steroids exhibiting induction of CYP3A activity and hepatomegaly associated with increased DNA synthesis
| Autor: | David F.V. Lewis, Costas Ioannides, R. Schulte-Hermann, Dennis V. Parke |
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| Rok vydání: | 2001 |
| Předmět: |
Quantitative structure–activity relationship
Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Quantitative Structure-Activity Relationship Receptors Cytoplasmic and Nuclear Biology Biochemistry Steroid Mixed Function Oxygenases chemistry.chemical_compound Endocrinology Cytochrome P-450 Enzyme System Demethylase activity medicine Cytochrome P-450 CYP3A Humans Molecular Biology DNA synthesis Cytochrome P450 Biological activity Oxidoreductases N-Demethylating Cell Biology DNA Ethylmorphine chemistry biology.protein Molecular Medicine Steroids Aryl Hydrocarbon Hydroxylases medicine.drug Hepatomegaly |
| Zdroj: | The Journal of steroid biochemistry and molecular biology. 74(4) |
| ISSN: | 0960-0760 |
| Popis: | The results of a quantitative structure–activity relationship (QSAR) study on a total of 14 steroids exhibiting induction of a CYP3A-associated activity and increase in liver weight/DNA synthesis is reported. It is found that different, but related, structural descriptors correlate with increase in ethylmorphine N -demethylase activity ( r =0.92) and with the increase in liver weight ( r =0.78) and DNA synthesis ( r =0.78). Although there is a strong correlation between increase in liver weight and DNA content ( r =0.999), neither of these correlated with ethylmorphine N -demethylase activity. These findings are discussed in the light of CYP3A induction, substrate specificity and inhibition; a proposed model of human CYP3A4 based on sequence homology with CYP102, a bacterial P450 of known crystal structure, demonstrates the possible mode of interaction between substrates and inhibitors within the putative active site. |
| Databáze: | OpenAIRE |
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