title: Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products.
abstract: 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.
authors.affiliation: 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.
authors.forename: Guiomar
authors.initials: G
authors.lastname: Pérez-Moreno
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Cantizani
authors.affiliation: 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.
authors.forename: Paula
authors.initials: P
authors.lastname: Sánchez-Carrasco
authors.affiliation: 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.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Ruiz-Pérez
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Martín
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Noureddine
authors.initials: N
authors.lastname: El Aouad
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pérez-Victoria
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: José Rubén
authors.initials: JR
authors.lastname: Tormo
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: González-Menendez
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: González
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: de Pedro
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Reyes
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Genilloud
authors.affiliation: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 34.18016-Armilla (Granada), Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.affiliation: 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.
authors.forename: Dolores
authors.initials: D
authors.lastname: González-Pacanowska
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013058:Mass Spectrometry; D010436:Pepstatins / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000962:Antimalarials; D001688:Biological Products; D010436:Pepstatins; D007770:L-Lactate Dehydrogenase; C031375:pepstatin