Natural Products as Leads in Schistosome Drug Discovery

Abstract

Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs) as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS) strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist

“…Natural product based drug discovery has provided critical breakthroughs in the treatment of parasitic disease (Shen, 2015), and there is considerable interest in mining the natural chemical lexicon to identify antischistosomal compounds (Neves et al., 2015). Here, we have studied the action of several aporphine alkaloid natural products (nuciferine, D-glaucine, boldine and bulbocapnine) on 5-HT signaling in schistosomes, which identified nuciferine as an effective inhibitor of GPCR signaling in vitro and 5-HT evoked motility responses in intact parasites.…”

Isolation and identification of two galangin metabolites from rat urine and determination of their <i>in vitro</i> hypolipidemic activity

“…Herbal medicines have been used in the treatment of obesity for past 100 decades [21,22]. Natural compounds with interesting structures and lipid regulating activities have attracted numerous attentions from chemists and pharmacologists [23].…”

Ultrastructural study of morphological changes in Schistosoma mansoni after in vitro exposure to the monoterpene rotundifolone

“…Therefore, the tegument is a critically important target for antischistosomal drugs 28 . Electron microscopic analyses, including TEM, have documented damage to the tegument of S. mansoni caused by exposure to synthetic and natural compounds 14 for various antischistosomal prototype compounds 29 .…”