Department of Biomedical Sciences, University of León, 24071 León, Spain.
Department of Chemistry, University of Puerto Rico, Río Piedras 00925-2537, San Juan, Puerto Rico.
Mar Drugs. 2020 Mar 31;18(4):187. doi: 10.3390/md18040187.
Neglected Tropical Diseases (NTD) represent a serious threat to humans, especially for those living in poor or developing countries. Almost one-sixth of the world population is at risk of suffering from these diseases and many thousands die because of NTDs, to which we should add the sanitary, labor and social issues that hinder the economic development of these countries. Protozoan-borne diseases are responsible for more than one million deaths every year. Visceral leishmaniasis, Chagas disease or sleeping sickness are among the most lethal NTDs. Despite not being considered an NTD by the World Health Organization (WHO), malaria must be added to this sinister group. Malaria, caused by the apicomplexan parasite , is responsible for thousands of deaths each year. The treatment of this disease has been losing effectiveness year after year. Many of the medicines currently in use are obsolete due to their gradual loss of efficacy, their intrinsic toxicity and the emergence of drug resistance or a lack of adherence to treatment. Therefore, there is an urgent and global need for new drugs. Despite this, the scant interest shown by most of the stakeholders involved in the pharmaceutical industry makes our present therapeutic arsenal scarce, and until recently, the search for new drugs has not been seriously addressed. The sources of new drugs for these and other pathologies include natural products, synthetic molecules or repurposing drugs. The most frequent sources of natural products are microorganisms, e.g., bacteria, fungi, yeasts, algae and plants, which are able to synthesize many drugs that are currently in use (e.g. antimicrobials, antitumor, immunosuppressants, etc.). The marine environment is another well-established source of bioactive natural products, with recent applications against parasites, bacteria and other pathogens which affect humans and animals. Drug discovery techniques have rapidly advanced since the beginning of the millennium. The combination of novel techniques that include the genetic modification of pathogens, bioimaging and robotics has given rise to the standardization of High-Performance Screening platforms in the discovery of drugs. These advancements have accelerated the discovery of new chemical entities with antiparasitic effects. This review presents critical updates regarding the use of High-Throughput Screening (HTS) in the discovery of drugs for NTDs transmitted by protozoa, including malaria, and its application in the discovery of new drugs of marine origin.
被忽视的热带病（NTD）对人类构成严重威胁，尤其是对生活在贫困或发展中国家的人而言。世界上近六分之一的人口面临这些疾病的风险，数千人因 NTD 而死亡，此外还有阻碍这些国家经济发展的卫生、劳动和社会问题。原生动物传播的疾病每年导致超过 100 万人死亡。内脏利什曼病、恰加斯病或昏睡病是最致命的 NTD 之一。尽管世界卫生组织（WHO）并不将疟疾视为 NTD，但必须将其添加到这个可怕的疾病群中。由顶复门寄生虫引起的疟疾每年导致数千人死亡。这种疾病的治疗方法一年比一年失去效果。由于疗效逐渐下降、固有毒性以及耐药性的出现或缺乏治疗依从性，目前许多使用的药物已经过时。因此，迫切需要新的药物。尽管如此，制药行业的大多数利益相关者表现出的兴趣寥寥，使得我们目前的治疗武器库匮乏，直到最近，寻找新药的工作都没有得到认真对待。这些疾病和其他疾病的新药来源包括天然产物、合成分子或重新利用药物。天然产物的最常见来源是微生物，例如细菌、真菌、酵母、藻类和植物，它们能够合成许多目前正在使用的药物（例如抗生素、抗肿瘤药、免疫抑制剂等）。海洋环境是另一个成熟的生物活性天然产物来源，最近在对抗寄生虫、细菌和其他影响人类和动物的病原体方面得到了应用。自千年之交以来，药物发现技术迅速发展。包括病原体基因修饰、生物成像和机器人技术在内的新型技术的结合，促成了高通量筛选平台在药物发现中的标准化。这些进展加速了具有抗寄生虫作用的新化学实体的发现。本文综述了高通量筛选（HTS）在发现原生动物传播的 NTD 药物（包括疟疾）方面的应用，以及其在海洋来源新药发现方面的应用。
