Abstract |
In this study, twenty hydroxylated and acetoxylated 3-phenylcoumarin derivatives were evaluated as inhibitors of immune complex-stimulated neutrophil oxidative metabolism and possible modulators of the inflammatory tissue damage found in type III hypersensitivity reactions. By using lucigenin- and luminol-enhanced chemiluminescence assays (CL-luc and CL-lum, respectively), we found that the 6,7-dihydroxylated and 6,7-diacetoxylated 3-phenylcoumarin derivatives were the most effective inhibitors. Different structural features of the other compounds determined CL-luc and/or CL-lum inhibition. The 2D-QSAR analysis suggested the importance of hydrophobic contributions to explain these effects. In addition, a statistically significant 3D-QSAR model built applying GRIND descriptors allowed us to propose a virtual receptor site considering pharmacophoric regions and mutual distances. Furthermore, the 3-phenylcoumarins studied were not toxic to neutrophils under the assessed conditions.
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Authors | Luciana M Kabeya, Carlos H T P da Silva, Alexandre Kanashiro, Joaquín M Campos, Ana Elisa C S Azzolini, Ana Cristina M Polizello, Mônica T Pupo, Yara M Lucisano-Valim |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 43
Issue 5
Pg. 996-1007
(May 2008)
ISSN: 0223-5234 [Print] France |
PMID | 17804122
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Antigen-Antibody Complex
- Coumarins
- Reactive Oxygen Species
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(chemistry, pharmacology)
- Antigen-Antibody Complex
(physiology)
- Coumarins
(chemistry, pharmacology)
- Female
- Hydrophobic and Hydrophilic Interactions
- In Vitro Techniques
- Luminescent Measurements
- Models, Molecular
- Neutrophils
(drug effects, metabolism)
- Quantitative Structure-Activity Relationship
- Rabbits
- Reactive Oxygen Species
(metabolism)
- Respiratory Burst
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