Binding to PLA2 May Contribute to the Anti-Inflammatory Activity of Catechol

• Published in: Chemical biology & drug design 2012-01, Vol.79 (1), p.143-147
• Main Authors: Dileep, Kalarickal V., Tintu, Ignatius, Mandal, Pradeep K., Karthe, Ponnuraj, Haridas, Madathilkovilakathu, Sadasivan, Chittalakkottu
• Format: Article
• Language: English
• Subjects: anti-inflammatory; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Binding Sites; Catalytic Domain; catechol; Catechols - chemistry; Catechols - pharmacology; Computer Simulation; crystal structure; Crystallography, X-Ray; enzyme inhibition; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Kinetics; Phospholipase A2 Inhibitors; Phospholipases A2 - chemistry; Phospholipases A2 - metabolism; PLA2; Protein Binding - drug effects
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2011.01258.x

Inhibiting PLA2 activity should, in theory, be an effective approach to control the inflammation. Several naturally occurring polyphenolic compounds have been reported as inhibitors of PLA2. Among the naturally occurring polyphenols, catechol (1,2‐dihydroxybenzene) possesses anti‐inflammatory activity. Catechol can inhibit cyclooxygenase and lipo‐oxygenase. By means of enzyme kinetic study, it was revealed that catechol can inhibit PLA2 also. Crystal structure showed that catechol binds to PLA2 at the opening of the active site cleft. This might stop the entry of substrate into the active site. Hence, catechol can be used as a lead compound for the development of novel anti‐inflammatory drugs with PLA2 as the target. Inhibition of PLA2 by catechol was not reported earlier. Enzyme kinetic study proved that catechol can inhibit PLA2. The crystal structure showed that catechol binds to PLA2 at the opening of the active site cleft and stop the entry of substrate into the active site.