Department of Biotechnology, Alagappa University, Karaikudi, 630 003, Tamil Nadu, India.
J Comput Aided Mol Des. 2012 Sep;26(9):1067-77. doi: 10.1007/s10822-012-9599-1. Epub 2012 Sep 18.
Drugs have been discovered in the past mainly either by identification of active components from traditional remedies or by unpredicted discovery. A key motivation for the study of structure based virtual screening is the exploitation of such information to design targeted drugs. In this study, structure based virtual screening was used in search for putative quorum sensing inhibitors (QSI) of Pseudomonas aeruginosa. The virtual screening programme Glide version 5.5 was applied to screen 1,920 natural compounds/drugs against LasR and RhlR receptor proteins of P. aeruginosa. Based on the results of in silico docking analysis, five top ranking compounds namely rosmarinic acid, naringin, chlorogenic acid, morin and mangiferin were subjected to in vitro bioassays against laboratory strain PAO1 and two more antibiotic resistant clinical isolates, P. aeruginosa AS1 (GU447237) and P. aeruginosa AS2 (GU447238). Among the five compounds studied, except mangiferin other four compounds showed significant inhibition in the production of protease, elastase and hemolysin. Further, all the five compounds potentially inhibited the biofilm related behaviours. This interaction study provided promising ligands to inhibit the quorum sensing (QS) mediated virulence factors production in P. aeruginosa.
在过去，药物主要是通过从传统药物中鉴定活性成分或意外发现而被发现的。基于结构的虚拟筛选研究的一个主要动机是利用这种信息来设计靶向药物。在这项研究中，基于结构的虚拟筛选被用于寻找铜绿假单胞菌的群体感应抑制剂（QSI）。虚拟筛选程序 Glide version 5.5 被应用于筛选 1920 种天然化合物/药物对铜绿假单胞菌 LasR 和 RhlR 受体蛋白的抑制作用。根据计算机对接分析的结果，五种排名最高的化合物分别是迷迭香酸、柚皮苷、绿原酸、桑色素和芒果苷，它们被用于针对实验室菌株 PAO1 以及两种更具抗生素耐药性的临床分离株铜绿假单胞菌 AS1（GU447237）和铜绿假单胞菌 AS2（GU447238）的体外生物测定。在研究的五种化合物中，除了芒果苷外，其他四种化合物在蛋白酶、弹性蛋白酶和溶血素的产生方面均表现出显著的抑制作用。此外，所有这五种化合物都有可能抑制生物膜相关的行为。这项相互作用的研究为抑制铜绿假单胞菌中群体感应（QS）介导的毒力因子的产生提供了有前景的配体。
