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Anti‐Inflammatory Property of n ‐Hexadecanoic Acid: Structural Evidence and Kinetic Assessment
Author(s) -
Aparna Vasudevan,
Dileep Kalarickal V.,
Mandal Pradeep K.,
Karthe Ponnuraj,
Sadasivan Chittalakkottu,
Haridas Madathilkovilakathu
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01418.x
Subject(s) - chemistry , isothermal titration calorimetry , phospholipase , phospholipase a , phospholipase a2 , enzyme , biochemistry , fatty acid
Ester bond hydrolysis of membrane phospholipids by Phospholipase A 2 and consequent release of fatty acids are the initiating steps of inflammation. It is proposed in this study that the inhibition of phospholipase A 2 is one of the ways to control inflammation. Investigations are carried out to identify the mode of inhibition of phospholipase A 2 by the n ‐hexadecanoic acid. It may help in designing of specific inhibitors of phospholipase A 2 as anti‐inflammatory agents. The enzyme kinetics study proved that n ‐hexadecanoic acid inhibits phospholipase A 2 in a competitive manner. It was identified from the crystal structure at 2.5 Å resolution that the position of n ‐hexadecanoic acid is in the active site of the phospholipase A 2 . The binding constant and binding energy have also been calculated using Isothermal Titration Calorimetry. Also, the binding energy of n ‐hexadecanoic acid to phospholipase A 2 was calculated by in silico method and compared with known inhibitors. It may be concluded from the structural and kinetics studies that the fatty acid, n ‐hexadecanoic acid, is an inhibitor of phospholipase A 2 , hence, an anti‐inflammatory compound. The inferences from the present study validate the rigorous use of medicated oils rich in n ‐hexadecanoic acid for the treatment of rheumatic symptoms in the traditional medical system of India, Ayurveda.