African @entity7246 , @entity232 , and @entity1526 are 3 neglected @entity66 for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography-mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included @entity4316 , @entity68277 , @entity28946 , @entity59703 , @entity68278 , and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

High-Throughput Screening Platform for Natural Product-Based Drug Discovery Against 3 Neglected Tropical Diseases: Human African Trypanosomiasis, XXXX , and @entity1526 .

@entity7246 :: ('MESH:D014352', 'Disease') :: ['trypanosomiasis'] @entity66 :: ('MESH:D004194', 'Disease') :: ['tropical diseases'] @entity68278 :: ('MESH:C465999', 'Chemical') :: ['hygrolidin'] @entity232 :: ('MESH:D007896', 'Disease') :: ['leishmaniasis'] @entity59703 :: ('MESH:D004448', 'Chemical') :: ['echinomycin'] @entity4316 :: ('MESH:D003609', 'Chemical') :: ['actinomycin D'] @entity1526 :: ('MESH:D014355', 'Disease') :: ['Chagas disease'] @entity68277 :: ('MESH:C052501', 'Chemical') :: ['bafilomycin B1'] @entity28946 :: ('MESH:D014128', 'Chemical') :: ['chromomycin A3']
@entity232 :: (MESH:D007896,Disease) :: ['Leishmaniasis']
