Novel sources of anthelmintics.
The G-series of naturally occurring compounds from Eucalyptus species contain representatives that are endoperoxides and Mannich bases. Mannich bases have been shown to be effective in killing protozoa in vitro. Previous studies of the role of cells of the immune system reveal that helminth parasites are susceptible to free radical attack. A 3-year research project studied the anthelmintic potential of endoperoxides and/or Mannich bases derived from G-compounds. Results from 1 series of synthetic analogues which show a positive relationship between chemical structure and anthelmintic activity are reported here. A G-Mannich base with an aromatic ring side chain as well as a long aliphatic side chain was the most active analogue in the series with an LD 50 < 0.1 mM in an in vitro larval motility assay. This work showed that Mannich bases are a potential source of compounds for parasite control. More work on formulation and pharmacokinetics is required to advance these compounds to the threshold of commercial production.
Bennet-Jenkins
E
E
Division of Biochemistry and Molecular Biology, Australian National University, Canberra, Australia.
Bryant
C
C
D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D005052:Eucalyptus; D005609:Free Radicals; D015511:Goat Diseases / Q000188:drug therapy; D006041:Goats; D006188:Haemonchiasis / Q000188:drug therapy / Q000662:veterinary; D006376:Helminths / Q000187:drug effects* / Q000378:metabolism; D008352:Mannich Bases / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010937:Plant Growth Regulators / Q000494:pharmacology; D010946:Plants, Medicinal; D013329:Structure-Activity Relationship
D000871:Anthelmintics; D005609:Free Radicals; D008352:Mannich Bases; D010936:Plant Extracts; D010937:Plant Growth Regulators