Binding of Quinoline-Based Inhibitors to <i>Plasmodium falciparum</i>Lactate Dehydrogenase: A Molecular Docking Study
Binding of Quinoline-Based Inhibitors to <i>Plasmodium falciparum</i>Lactate Dehydrogenase: A Molecular Docking Study作者机构：Department of Chemistry & Biochemistry University of Notre Dame Notre Dame USA School of Natural Sciences Indiana University Southeast New Albany USA
出 版 物：《Open Journal of Biophysics》 (生物物理学期刊（英文）)
年 卷 期：2013年第3卷第4期
页 面：285-290页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Quinoline-Based Inhibitors Molecular Docking Plasmodium falciparum
摘 要：Development of new antimalarial drugs continues to be of great importance due to the resistance of the malaria parasite to currently used drugs. Glycolytic enzymes have emerged as potential targets for the development of new drugs due to the reliance of the parasite on glycolysis for energy. In this study, molecular docking was used to study the binding of some quinoline-based drugs to the glycolytic enzyme lactate dehydrogenase. The docking studies identified two potential binding sites for each ligand, one of them being the cofactor-binding site. For all ligands studied, there was the comparable binding to the cofactor-binding site as well as the secondary binding site when the cofactor was absent. All ligands showed significantly lower binding affinity than NADH for the cofactor binding site. The alternative site was the site of preference when docking was done in the presence of the cofactor. While binding to the cofactor site may support other studies suggesting potential for competitive inhibition, the fact that the binding affinities of all the ligands are significantly lower than that for NADH in this site suggests that these ligands will be ineffective competitive inhibitors. The identification of an alternative binding site with comparable affinity that is not affected by the presence of the cofactor may suggest the possibility of non-competitive inhibition that requires further exploration.
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