Developing novel anthelmintics from plant cysteine proteinases

Abstract

Intestinal helminth infections of livestock and humans are predominantly controlled by treatment with three classes of synthetic drugs, but some livestock nematodes have now developed resistance to all three classes and there are signs that human hookworms are becoming less responsive to the two classes (benzimidazoles and the nicotinic acetylcholine agonists) that are licensed for treatment of humans. New anthelmintics are urgently needed, and whilst development of new synthetic drugs is ongoing, it is slow and there are no signs yet that novel compounds operating through different modes of action, will be available on the market in the current decade. The development of naturally-occurring compounds as medicines for human use and for treatment of animals is fraught with problems. In this paper we review the current status of cysteine proteinases from fruits and protective plant latices as novel anthelmintics, we consider some of the problems inherent in taking laboratory findings and those derived from folk-medicine to the market and we suggest that there is a wealth of new compounds still to be discovered that could be harvested to benefit humans and livestock.

EVOLUTION IN CHEMOTHERAPY OF HUMAN AND ANIMAL HELMINTHIASES (review)

“…They may have different chemical nature -mono-and polycyclic (condensed and uncondensed), aromatic (e.g., polyhydric phenols -vegetable tannins), and heterocyclic (e.g., fervenulin) compounds, flavonoids, lactones, alkaloids, terpenoids, peptides, etc. Discovery of new substances with anthelmintic properties is suggested by numerous recent reports: fungichromine B (28-membered polyene macrolide product of actinomycete Streptomyces albogriseolus HA10002, effective against tuber nematode) (110), fervenulin (109), nafuredin (product of Aspergillus niger FT-0554) (111), bacterial protein Cry5B (Bacillus thuringiensis) (112), cysteine proteases of pineapple, papaya, and some other plants (113), alkaloids of marine bryozoans (114), other substances (115).…”

Anthelmintic evaluation of Cucurbita pepo againstgastrointestinal nematodes of sheep

“…This infection is generally controlled by synthetic drugs and vaccination (Behnke et al, 2008). Development of drug resistance in the parasites, lack of new anthelmintics, the high cost of existent ones, and the possibility of their chemical residues in animal products demand alternative, feasible, and environmentally innocuous control methods that meet consumers' demands and fit the needs of farmers (Ademola and Eloff, 2010).…”

Photodegradation of carbendazim sensitized by aromatic ketones

“…Carbendazim (1, Chart 1) is a member of the benzimidazole (BZ) family, which includes a series of heterocyclic compounds extensively used as broad spectrum anthelmintic, anti-nematodal and anti-protozoal agents, [1][2][3][4][5] as well as post-harvest fungicides on fruits and vegetables. [6][7][8] The extensive use of 1(12000 tons/year) and related BZs has led to the development of resistance, which is usually triggered by mutation(s) in a single chromosomal β-tubulin gene.…”