Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Comparative MO-QSAR studies in various species including man

B Tyrakowska1, N H Cnubben, A E Soffers

  • 1Faculty of Commodity Science, Poznań University of Economics, Poland.

Chemico-Biological Interactions
|March 25, 1996
PubMed
Summary

Quantitative structure-activity relationships (QSARs) for cytochrome P450 biotransformation in rats can predict pathways in other species, including humans. Molecular orbital (MO)-QSARs effectively forecast aromatic hydroxylation regioselectivity and rates across diverse mammalian models.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Is the sentinel lymph node pathology protocol in breast cancer patients associated with the risk of regional recurrence?

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·2013
Same author

The interplay of glutathione-related processes in antioxidant defense.

Environmental toxicology and pharmacology·2011
Same author

Towards a more standardized assessment of diagnostic tumor-markers.

International journal of oncology·2011
Same author

Glutathione, glutathione-s-transferase and p-170 glycoprotein in metastases of malignant melanomas.

International journal of oncology·2011
Same author

The effect of zymosan-induced generalized inflammation on tumor-growth in a rat renal-cell carcinoma model.

International journal of oncology·2011
Same author

Conclusiveness of fine needle aspiration in 2419 histologically confirmed benign and malignant breast lesions.

Breast (Edinburgh, Scotland)·2011

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Computational Chemistry
  • Toxicology

Background:

  • Cytochrome P450 enzymes are crucial for metabolizing xenobiotics, including benzene derivatives.
  • Quantitative structure-activity relationships (QSARs) are used to predict metabolic pathways.
  • Extrapolation of QSAR models across species is essential for understanding drug metabolism and toxicity.

Purpose of the Study:

  • To determine if molecular orbital (MO)-QSARs developed for Wistar rats can predict cytochrome P450-catalyzed biotransformation in other species, including humans.
  • To validate the predictive power of MO-QSARs for in vivo and in vitro aromatic hydroxylation of benzene derivatives.
  • To assess the applicability of MO-QSARs for predicting biotransformation rates and regioselectivity across different mammalian liver microsomes.

Related Experiment Videos

Main Methods:

  • Calculation of molecular orbital substrate characteristics, specifically electron density distribution and E(HOMO) values.
  • Quantitative structure-activity relationship (QSAR) modeling using these calculated parameters.
  • Experimental validation using in vivo and in vitro biotransformation assays with liver microsomes from rats, mice, rabbits, guinea pigs, and humans.

Main Results:

  • MO-QSARs accurately predicted the regioselectivity of in vivo aromatic hydroxylation for fluorobenzene derivatives across tested animal species.
  • In vitro hydroxylation of 3-fluoroaniline showed minimal species-dependent variation, primarily governed by substrate reactivity characteristics.
  • High correlation coefficients (≥0.97) were achieved when extrapolating MO-QSARs for aniline derivative hydroxylation rates to various species, including humans.

Conclusions:

  • MO-QSARs previously established for Wistar rats are highly extrapolatable to other species, including mice, rabbits, guinea pigs, and humans.
  • The biotransformation of benzene derivatives by mammalian cytochrome P450 enzymes is predominantly dictated by substrate chemical reactivity parameters.
  • MO-based QSARs derived from rat studies offer a reliable basis for predicting cytochrome P450-mediated biotransformation pathways in diverse species.