Sinha Shweta, Sarma Phulen, Sehgal Rakesh, Medhi Bikash
Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Front Pharmacol. 2017 Oct 23;8:754. doi: 10.3389/fphar.2017.00754. eCollection 2017.
The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000-2,000,000 compounds per screening campaign), before pre-clinical trials to select optimum lead. Carrying out screening of antimalarials is very difficult as different assay methods are subject to numerous sources of variability across different laboratories around the globe. Despite this, screening is an essential part of antimalarial drug development as it enables to resource various confounding factors such as host immune response and drug-drug interaction. Therefore, in this article, we try to illustrate the basic necessity behind study and how new methods are developed and subsequently adopted for high-throughput antimalarial drug screening and its application in achieving the next level of screening based on the current approaches (such as stem cells).
耐药性的出现和传播是疟疾根除任务中的主要挑战。除了世界卫生组织制定的各种策略,如病媒管理、源头减少、早期病例检测、及时治疗以及开发新的诊断方法和疫苗外,开发新型高效抗疟药物的需求已成为全球疟疾研究议程上的关键优先事项。在几个筛选阶段,要对数以百万计的化合物进行筛选(每次筛选活动筛选1000 - 2000000种化合物),然后进行临床前试验以选择最佳先导化合物。由于不同的检测方法在全球不同实验室中存在众多变异性来源,因此开展抗疟药物筛选非常困难。尽管如此,筛选仍是抗疟药物研发的重要组成部分,因为它能够应对各种混杂因素,如宿主免疫反应和药物相互作用。因此,在本文中,我们试图阐述该研究背后的基本必要性,以及如何开发新方法并随后将其应用于高通量抗疟药物筛选,以及基于当前方法(如干细胞)在实现更高水平筛选方面的应用。