Pérez-Moreno Guiomar, Cantizani Juan, Sánchez-Carrasco Paula, Ruiz-Pérez Luis Miguel, Martín Jesús, El Aouad Noureddine, Pérez-Victoria Ignacio, Tormo José Rubén, González-Menendez Víctor, González Ignacio, de Pedro Nuria, Reyes Fernando, Genilloud Olga, Vicente Francisca, González-Pacanowska Dolores
Instituto de Parasitología y Biomedicina "López-Neyra", Consejo Superior de Investigaciones Científicas, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, s/n, 18016-Armilla (Granada), Spain.
Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
PLoS One. 2016 Jan 6;11(1):e0145812. doi: 10.1371/journal.pone.0145812. eCollection 2016.
Due to the low structural diversity within the set of antimalarial drugs currently available in the clinic and the increasing number of cases of resistance, there is an urgent need to find new compounds with novel modes of action to treat the disease. Microbial natural products are characterized by their large diversity provided in terms of the chemical complexity of the compounds and the novelty of structures. Microbial natural products extracts have been underexplored in the search for new antiparasitic drugs and even more so in the discovery of new antimalarials. Our objective was to find new druggable natural products with antimalarial properties from the MEDINA natural products collection, one of the largest natural product libraries harboring more than 130,000 microbial extracts. In this work, we describe the optimization process and the results of a phenotypic high throughput screen (HTS) based on measurements of Plasmodium lactate dehydrogenase. A subset of more than 20,000 extracts from the MEDINA microbial products collection has been explored, leading to the discovery of 3 new compounds with antimalarial activity. In addition, we report on the novel antiplasmodial activity of 4 previously described natural products.
由于目前临床可用的抗疟药物结构多样性较低，且耐药病例不断增加，迫切需要寻找具有新作用模式的新化合物来治疗该疾病。微生物天然产物的特点是其化合物的化学复杂性和结构新颖性所带来的高度多样性。在寻找新的抗寄生虫药物方面，微生物天然产物提取物尚未得到充分探索，在发现新的抗疟药物方面更是如此。我们的目标是从MEDINA天然产物库中寻找具有抗疟特性的新的可成药天然产物，MEDINA是最大的天然产物库之一，拥有超过13万种微生物提取物。在这项工作中，我们描述了基于疟原虫乳酸脱氢酶测量的表型高通量筛选（HTS）的优化过程和结果。我们对MEDINA微生物产物库中超过20000种提取物的一个子集进行了探索，发现了3种具有抗疟活性的新化合物。此外，我们还报告了4种先前描述的天然产物的新型抗疟活性。
