Phenolic Metabolites of <i>Dalea ornata</i> Affect Both Survival and Motility of the Human Pathogenic Hookworm <i>Ancylostoma ceylanicum</i>

Hookworms are ubiquitous human parasites, infecting nearly one billion people worldwide, and are the leading cause of anemia and malnutrition in resource-limited countries. Current drug treatments rely on the benzimidazole derivatives albendazole and mebendazole, but there is emerging resistance to these drugs. As part of a larger screening effort, using a hamster-based ex vivo assay, anthelmintic activity toward <i>Ancylostoma ceylanicum</i> was observed in the crude extract of aerial parts of <i>Dalea ornata</i>. These studies have led to the isolation and characterization of phenolic metabolites <b>1</b>–<b>10</b>. The structures were determined by 1D and 2D NMR spectroscopy, and the absolute configuration of <b>1</b> was assigned using electronic circular dichroism data. The new compound, (2<i>S</i>)-8-(3-methylbut-2-en-1-yl)-6,7,4′-trihydroxyflavanone (<b>1</b>), was weakly active at 7.3 μM, with 17% reduction in survival of the hookworms after 5 days. The rotenoids deguelin (<b>9</b>) and tephrosin (<b>10</b>), predictably perhaps, were the most active, with complete worm mortality observed by day 4 (or earlier) at 6.3 and 6.0 μM, respectively. The effects of <b>1</b>–<b>10</b> on hookworm motility and on toxicity to hamster splenocytes were also explored as important measures of treatment potential