An appraisal of natural products active against parasitic nematodes of animals

Abstract

Here, the scientific and patent literature on the activities of purified natural compounds has been reviewed, with the aim of assessing their suitability as anthelmintic drug discovery starting points. Only compounds described as active against parasitic nematodes of animals or against the model nematode Caenorhabditis elegans have been analysed. Scientific articles published since 2010 and patents granted from 2000, both inclusive, have been included in this analysis. The results show a scarcity of novel chemical structures, a limited follow-up of compounds disclosed before 2010 and a bias towards the screening of plant products, almost to the exclusion of other sources, when microbial extracts have, historically, provided most starting points for anti-infective drugs. All plant products published in this period were previously known, alerting to the high re-discovery rates of a limited number of chemical classes from this source. The most promising compounds described in the literature reviewed here, namely the linear nemadectin-derivatives, are novel and of bacterial origin. Patented but otherwise unpublished spiroketal structures also appear as interesting scaffolds for future development. The patent literature confirmed that it is possible to patent derivatives of previously known products, making them valid starting points for translational research.

Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics

“…Of course, this does not account for situations where there may be advantages to enabling reduced drug dose due to intestinal reabsorption of drugs excreted via the bile ( Alvarez-Bujidos et al, 1998 ). It is also unclear whether a product for blood-feeding nematodes (such as hookworm species) needs to be available in the blood at therapeutic levels for efficacy ( Garcia-Bustos et al, 2019 ). Furthermore, given that many worms are found in tissues other than the gastrointestinal tract, the desire for a broad-spectrum anthelmintic may negate this advantage.…”

“…A casual PubMed search using the keywords ‘natural product anthelmintic’ yields over two thousand results. However as noted by Garcia-Bustos et al (2019) there has been a strong bias towards plant extracts with few of the active compounds identified and even more limited follow-up post initial description. The lack of follow-through is a key area of weakness in current anthelmintic discovery; more funding and incentive through industry, academic and stakeholder partnerships is needed to develop these discoveries beyond simple screening.…”

Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence

“…Parasitic helminth infections in small ruminates can be economically devastating to farmers [130]. The resistance of gastrointestinal nematodes to synthetic anthelmintic and the high costs associated with the use of those compounds led researchers to seek alternative methods of control [131,132]. Extracts from P. juliflora leaf and root bark samples were evaluated for in vitro activity against mixed samples of gastrointestinal nematodes (Haemonchus contortus, Trichostrongylus spp.…”

Combating Parasitic Nematode Infections, Newly Discovered Antinematode Compounds from Marine Epiphytic Bacteria

“…Humans are vulnerable to infectious diseases caused by parasitic helminths (nematodes) resulting in morbidity and mortality within the population [ 1 , 2 , 3 ]. Approximately 24% of the global human population, corresponding to 1.5 billion people, suffer from parasitic helminth infections [ 4 ]. There are almost 300 nematodes associated with zoonotic diseases that are able to infect humans, including some of the most devastating parasites such as Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), Gnathostoma spinigerum , Halicephalobus gingivalis and Trichinella spiralis (Trichina worm) [ 1 , 5 , 6 ].…”

“…Given the impacts of resistant parasitic nematodes to human and economic growth, novel antinematode chemotherapeutic agents are urgently needed as a preventive control against parasite infestation [ 4 , 50 ]. For decades, microorganisms, particularly bacteria, have served as a precious source for bioactive compounds, some of which have been developed into novel drugs including those with nematicidal activity [ 51 , 52 ].…”