An Appraisal of Natural Products Active Against Parasitic Nematodes of Animals

Author: mycolabadmin
2019-06-17
View Source

Summary

This review examined natural compounds that could potentially be developed into new drugs to treat parasitic worm infections in humans and animals. The researchers found relatively few promising new compounds, with most studies focusing on plant sources despite bacteria historically providing better drug candidates. The findings have important implications for addressing growing drug resistance in parasitic worm treatments. Key impacts on everyday life: • Growing resistance to existing dewormers threatens both human health and livestock production • New drug development is crucial to maintain effective treatment options for parasitic infections • Natural compounds remain an important source of potential new medicines • Better research infrastructure could accelerate discovery of new treatments • Sustainable sourcing of natural compounds affects medicine availability and cost

Background

Parasitic helminths of humans and other animals cause diseases of major socio-economic importance globally. Parasitic nematodes have a massive impact on human health, with WHO estimating ~1.5 billion people were infected with intestinal worms in 2018. These parasites also cause substantial morbidity and mortality in domesticated and wild animals worldwide, leading to major losses in global food production annually. Control relies heavily on anthelmintic drugs, but widespread resistance has emerged, creating an urgent need for new treatments.

Objective

To critically review the scientific and patent literature on purified natural compounds active against parasitic nematodes of animals or the model nematode Caenorhabditis elegans, assessing their suitability as anthelmintic drug discovery starting points. The review covered scientific articles published since 2010 and patents granted from 2000.

Results

The review revealed a scarcity of novel chemical structures and limited follow-up of previously disclosed compounds. There was a strong bias toward screening plant products, despite microbial extracts historically providing most anti-infective drug starting points. All plant products published in this period were previously known compounds. The most promising new compounds were linear nemadectin derivatives of bacterial origin. Some patented but unpublished spiroketal structures also showed potential as scaffolds for development.

Conclusion

The findings were disappointing given that natural products are typically a main source of novel drug scaffolds. Only one new chemical class emerged from the scientific literature – the open nemadectin analogues. Most publications reported compounds with low to moderate activity from previously unexplored sources but yielded known chemical structures. The focus on plant sources appears suboptimal, as bacterial sources have historically provided more successful anthelmintic compounds. Better screening infrastructure and funding are needed to enable more productive natural product discovery efforts.

Published in:Parasites & Vectors,
Study Type:Review,
Source: 10.1186/s13071-019-3537-1