Mechanism of action in a 4,5-diarylpyrrole series of selective cyclo-oxygenase-2 inhibitors

Using semi-empirical AM1 calculation and 6.31G∗ basis sets, we have calculated the energy of the highest-occupied molecular orbital (E HOMO) for anti-inflammatory 4,5-diarylpyrroles which have been shown to have inhibitory activity on cyclooxygenase COX-2, an inducible enzyme expressed during inflam...

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Bibliographic Details
Published in:Free radical biology & medicine 2000-06, Vol.28 (11), p.1638-1641
Main Authors: Zoete, Vincent, Maglia, Francesca, Rougée, Michel, Bensasson, René V
Format: Article
Language:English
Subjects:
5-diarrylpyrroles
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - chemistry
Cyclooxygenase Inhibitors - pharmacology
Energy of the highest occupied molecular orbital/lipophilicity/Cyclooxygenase-2 and -1 inhibitions
Free radicals
In Vitro Techniques
Isoenzymes - antagonists & inhibitors
Isoenzymes - pharmacology
Oxidation-Reduction
Prostaglandin-Endoperoxide Synthases - pharmacology
Pyrroles - chemistry
Pyrroles - pharmacology
Structure-Activity Relationship
Thermodynamics
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Summary:Using semi-empirical AM1 calculation and 6.31G∗ basis sets, we have calculated the energy of the highest-occupied molecular orbital (E HOMO) for anti-inflammatory 4,5-diarylpyrroles which have been shown to have inhibitory activity on cyclooxygenase COX-2, an inducible enzyme expressed during inflammation. We have found a correlation between the E HOMO of a molecule and its COX-2 inhibition. However, no correlation was observed between E HOMO and the inhibition efficiency of cyclooxygenase-1 (COX-1), the constitutively expressed enzyme, protective to the organism. This result suggests that the inhibitions of the two isoforms follow different molecular mechanisms.
ISSN:0891-5849
1873-4596
DOI:10.1016/S0891-5849(00)00278-1