Abstract
Schistosomiasis is a chronic parasitic disease caused by trematodes of the genus Schistosoma; it is commonly caused by Schistosoma mansoni, which is transmitted by Bioamphalaria snails. Studies show that more than 200 million people are infected and that more than 90% of them live in Africa. Treatment with praziquantel has the best cost–benefit result on the market. However, hypersensitivity, allergy, and drug resistance are frequently presented after administration. From this perspective, ligand-based and structure-based virtual screening (VS) techniques were combined to select potentially active alkaloids against S. mansoni from an internal dataset (SistematX). A set of molecules with known activity against S. mansoni was selected from the ChEMBL database to create two different models with accuracy greater than 84%, enabling ligand-based VS of the alkaloid bank. Subsequently, structure-based VS was performed through molecular docking using four targets of the parasite. Finally, five consensus hits (i.e., five alkaloids with schistosomicidal potential), were selected. In addition, in silico evaluations of the metabolism, toxicity, and drug-like profile of these five selected alkaloids were carried out. Two of them, namely, 11,12-methylethylenedioxypropoxy and methyl-3-oxo-12-methoxy-n(1)-decarbomethoxy-14,15-didehydrochanofruticosinate, had plausible toxicity, metabolomics, and toxicity profiles. These two alkaloids could serve as starting points for the development of new schistosomicidal compounds based on natural products.
Highlights
Neglected tropical diseases (NTDs) are a global public health concern
Schistosomiasis is a chronic parasitic disease caused by trematodes of the genus Schistosoma, where the most common causes of the disease are Schistosoma mansoni and Schistosoma haematobium, which are transmitted by Bioamphalaria and Bulinus snails, respectively
The bank of molecules with known activity against S. mansoni and the alkaloids isolated from the Menispermaceae and Apocynaceae families were described using five different molecular descriptor types and predictions were made using models built following the best practices of QSAR modeling [30,50]
Summary
Neglected tropical diseases (NTDs) are a global public health concern. Most prevalent in Latin America, Africa, and Southeast Asia, NTDs generally affect the poorest populations, which are living in lower sanitary and socioeconomic conditions. Health Organization, there are 17 major parasitic infections, of which, the neglected tropical diseases are schistosomiasis, leishmaniasis, trachoma, lymphatic filariasis, and Chagas diseases [1,2,3]. Schistosomiasis is a chronic parasitic disease caused by trematodes of the genus Schistosoma, where the most common causes of the disease are Schistosoma mansoni and Schistosoma haematobium, which are transmitted by Bioamphalaria and Bulinus snails, respectively. Studies show more than 200 million people are infected with Schistosoma and that more than. Numerous studies have suggested praziquantel to be safe, efficacious, and cost-effective [8].
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