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Quantitative structure-activity relationship study on some dihydropteridine reductase inhibitors
R Babbar1, J K Gupta, S P Gupta
1Department of Chemistry, Birla Institute of Technology and Science, Pilani, India.
Journal of Enzyme Inhibition
|January 1, 1989
Summary
Dihydropteridine reductase (DHPR) inhibition potency correlates with molecular properties. Electron-donating substituents enhance inhibition, while large substituents hinder it due to steric effects.
Area of Science:
- Medicinal Chemistry
- Biochemistry
- Molecular Pharmacology
Background:
- Dihydropteridine reductase (DHPR) is a crucial enzyme in folate metabolism.
- Understanding the structure-activity relationships of DHPR inhibitors is vital for drug development.
Purpose of the Study:
- To analyze the DHPR inhibitory potencies of phenylpyridine derivatives.
- To correlate inhibitory activity with physico-chemical and molecular properties.
Main Methods:
- Quantitative Structure-Activity Relationship (QSAR) analysis.
- Correlation of inhibitory data with Hammett constant (sigma) and van der Waals volume (Vw).
Main Results:
- Significant linear correlation found between DHPR inhibition and Hammett constant (sigma).
- Significant parabolic correlation observed between DHPR inhibition and van der Waals volume (Vw).
- Inhibition is enhanced by electron-donating substituents and hindered by sterically bulky ones at specific positions.
Conclusions:
- DHPR inhibition involves dispersion interactions.
- Molecular electronic and steric properties, particularly at specific substituent positions, significantly influence DHPR inhibitory activity.