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

Abstract

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 Ancylostoma ceylanicum was observed in the crude extract of aerial parts of Dalea ornata. These studies have led to the isolation and characterization of phenolic metabolites 1–10. The structures were determined by 1D and 2D NMR spectroscopy, and the absolute configuration of 1 was assigned using electronic circular dichroism data. The new compound, (2S)-8-(3-methylbut-2-en-1-yl)-6,7,4′-trihydroxyflavanone (1), was weakly active at 7.3 µM, with 17% reduction in survival of the hookworms after 5 days. The rotenoids deguelin (9) and tephrosin (10), 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 1–10 on hookworm motility and on toxicity to hamster splenocytes were also explored as important measures of treatment potential.

Digital Database of Absorption Spectra of Diverse Flavonoids Enables Structural Comparisons and Quantitative Evaluations

“…Absorption spectral data (molar absorption coefficients, absorption maxima, solvents, and literature citations) are listed in Table and the Supporting Information (Table S1) for all 177 flavonoids. ,,,,− …”

Comparison of percutaneous vs oral infection of hamsters with the hookworm Ancylostoma ceylanicum: Parasite development, pathology and primary immune response

“…Studies using the hamster model suggest that oral infections with Ancylostoma ceylanicum [26,41] closely approximate some observations made in human infections [27,31,32,43], which has added to our understanding of hookworm pathogenesis and the host-parasite interaction. Establishment of patent A. ceylanicum infections in outbred Golden Syrian hamsters has made possible detailed characterizations of hookworm disease pathogenesis [27], evaluation of therapeutic interventions [36,[44][45][46][47], vaccine development [27,[48][49][50][51][52][53][54], and characterization of innate/ acquired immune responses [31,34,35,45].…”

“…Establishment of patent A . ceylanicum infections in outbred Golden Syrian hamsters has made possible detailed characterizations of hookworm disease pathogenesis [ 27 ], evaluation of therapeutic interventions [ 36 , 44 – 47 ], vaccine development [ 27 , 48 – 54 ], and characterization of innate/acquired immune responses [ 31 , 34 , 35 , 45 ].…”