Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Palayad PO, Kerala, 670661, India.
Interdiscip Sci. 2011 Sep;3(3):189-97. doi: 10.1007/s12539-011-0090-9. Epub 2011 Sep 29.
The enzyme phospholipase A2 is responsible for the hydrolysis of membrane phospholipids that release arachidonic acid, which serves as a substrate for pro-inflammatory mediators, such as prostaglandins and leucotriens. The binding of the substrate to PLA2 occurs through a well-formed hydrophobic channel. So blocking the hydrophobic channel is an effective way to inhibit PLA2. Compounds inhibiting PLA2 have been implicated as potential therapeutic agents in the treatment of inflammation related diseases. Curcumin is a well studied compound isolated from the plant Curcuma longa. The PLA2 inhibiting activity of curcumin has been studied in our laboratory. The present study focuses whether any of the curcumin analogs can bind PLA2 more strongly than curcumin. To check this, binding of twenty eight different curcumin analogs to PLA2 have been studied by molecular modeling and docking. The mode of interactions of compounds with strong binding are discussed and reported here. It has been observed that four analogs namely rosmarinic acid, tetrahydrocurcumin, dihydrocurucmin and hexahydrocurcumin possess better binding energy than curcumin. The present study may lead to the better understanding of PLA2 inhibition by curcumin analogs. This may help to develop better anti-inflammatory drugs.
酶磷脂酶 A2 负责水解膜磷脂，释放花生四烯酸，后者可作为促炎介质（如前列腺素和白三烯）的底物。底物与 PLA2 的结合是通过一个形成良好的疏水性通道发生的。因此，阻断疏水性通道是抑制 PLA2 的有效方法。抑制 PLA2 的化合物已被认为是治疗炎症相关疾病的潜在治疗剂。姜黄素是从植物姜黄中分离得到的一种研究充分的化合物。我们实验室研究了姜黄素对 PLA2 的抑制活性。本研究重点研究是否有任何姜黄素类似物比姜黄素更能与 PLA2 结合。为了检查这一点，通过分子建模和对接研究了二十八种不同的姜黄素类似物与 PLA2 的结合。本文讨论并报告了具有强结合能力的化合物的相互作用模式。结果表明，四种类似物，即迷迭香酸、四氢姜黄素、二氢姜黄素和六氢姜黄素，具有比姜黄素更好的结合能。本研究可能有助于更好地理解姜黄素类似物对 PLA2 的抑制作用。这可能有助于开发更好的抗炎药物。
