title: 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.
authors: Kaitlin
authors: K
authors: Deardorff
authors: William
authors: W
authors: Ray
authors: Eric
authors: E
authors: Winterstein
authors: MacKenzie
authors: M
authors: Brown
authors: Jocelyn
authors: J
authors: McCornack
authors: Brianda
authors: B
authors: Cardenas-Garcia
authors: Kiah
authors: K
authors: Jones
authors: Sarah
authors: S
authors: McNutt
authors: Shannon
authors: S
authors: Fulkerson
authors: Department of BioMolecular Sciences, Division of Pharmacognosy, and the Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi , University, Mississippi 38677, United States.
authors: Daneel
authors: D
authors: Ferreira
authors: Department of Drug Discovery and Biomedical Sciences, The Medical University of South Carolina , Charleston, South Carolina 29425, United States.
authors: Charlotte
authors: C
authors: Gény
authors: Department of Drug Discovery and Biomedical Sciences, The Medical University of South Carolina , Charleston, South Carolina 29425, United States.
authors: Xiaoyan
authors: X
authors: Chen
authors: Gil
authors: G
authors: Belofsky
authors: Blaise
authors: B
authors: Dondji
mesh_terms: D015766:Albendazole / Q000737:chemistry / Q000494:pharmacology; D000722:Ancylostoma / Q000737:chemistry*; D000723:Ancylostomatoidea / Q000737:chemistry*; D000724:Ancylostomiasis / Q000188:drug therapy; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000494:pharmacology*; D006224:Cricetinae; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry; D006801:Humans; D008463:Mebendazole / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D035261:Plant Components, Aerial / Q000737:chemistry; D027824:Rosaceae / Q000737:chemistry; D031995:Saxifragaceae / Q000737:chemistry; D013154:Spleen / Q000166:cytology* / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D010636:Phenols; D008463:Mebendazole; D015766:Albendazole