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 Patented but otherwise unpublished spiroketal structures also appear as interesting scaffolds for future development.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.

Keywords: Animals; Anthelmintics; Natural products; Nematocides.

Fig. 1

Examples of currently used nematocides

Fig. 2

Phenols

Fig. 3

Cinnamoyl derivatives and polyphenols (tannins, flavonoids and isoflavonoids)

Fig. 4

Polyphenols (cont.) (tannins, flavonoids and isoflavonoids)

Fig. 5

Terpenes (terpenoids or isoprenoids)

Fig. 6

Prenyl derivatives (linear terpenes and terpenoids)

Fig. 7

Triterpenoids and triterpenoid glycosides (saponins)

Fig. 8

Macrocycles and analogues

Fig. 9

Miscellaneous compounds

Fig. 10

Patented nematocidal natural products (2000–2018)