Effects of Novel Diarylpentanoid Analogues of Curcumin on Secretory Phospholipase A2, Cyclooxygenases, Lipo‐oxygenase, and Microsomal Prostaglandin E Synthase‐1. (14th May 2014)

• Record Type: Journal Article
• Authors: Ahmad, Waqas; Kumolosasi, Endang; Jantan, Ibrahim; Bukhari, Syed N. A.; Jasamai, Malina
• Is Part Of: Chemical biology & drug design. Volume 83:Number 6(2014:Jun.)
• Page Start: 670
• Page End: 681
• Publication Date: 2014-05-14
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12280
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12280-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Arachidonic acid and its metabolites have generated a heightened interest due to their significant role in inflammation. Inhibiting the enzymes involved in arachidonic acid metabolism has been considered as the synergistic anti‐inflammatory effect. A series of novel curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on activity of secretory phospholipase A<sub>2</sub>, cyclooxygenases, soybean lipo‐oxygenase as well as microsomal prostaglandin E synthase‐1. Among the curcumin analogues, compounds <bold>3</bold>, <bold> 6</bold>, <bold> 9</bold>, <bold> 12, </bold> and <bold>17</bold> exhibited strong inhibition of secretory phospholipase A<sub>2</sub> activity, with IC<sub>50</sub> values ranging from 5.89 to 11.02 <italic>μ</italic><sc>m</sc>. Seven curcumin analogues <bold>1</bold>, <bold> 3</bold>, <bold> 6</bold>, <bold> 7</bold>, <bold> 9</bold>, <bold> 11, </bold> and <bold>12</bold> showed inhibition of cyclooxygenases‐2 with IC<sub>50</sub> values in the range of 46.11 to 94.86 <italic>μ</italic><sc>m</sc>, which were lower than that of curcumin. Compounds <bold>3</bold>, <bold> 6</bold>, <bold> 7</bold>, <bold> 12, </bold> and <bold>17</bold> showed strong inhibition of lipo‐oxygenase enzyme activity. Preliminary screening of diarylpentanoid curcumin analogues for microsomal prostaglandin E synthase‐1 activity revealed that four diarylpentanoid curcumin analogues <bold>5</bold>, <bold> 6</bold>, <bold> 7</bold>, and <bold>13</bold> demonstrated higher inhibition of microsomal prostaglandin E synthase‐1 activity with IC<sub>50</sub> ranging from 2.41 to 4.48 <italic>μ</italic><sc>m</sc>, which was less than that of curcumin. The present results suggest that some of these diarylpentanoid analogues were able to inhibit the activity of these enzymes. This raises the possibility that diarylpentanoid analogues of curcumin might serve as useful starting point for the design of improved anti‐inflammatory agents.</p> </abstract>