Synthesis and activity of substituted anthraquinones against a human filarial parasite, Brugia malayi. J Med Chem 2005 Apr 21;48(8):2822-30
Date
04/15/2005Pubmed ID
15828820DOI
10.1021/jm0492655Scopus ID
2-s2.0-17444392875 (requires institutional sign-in at Scopus site) 68 CitationsAbstract
Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Here we report the synthesis of novel anthraquinones A-S and their antifilrarial activity. Anthraquinones A-S were synthesized by a single-step Friedel-Crafts acylation reaction between phthalic anhydrides and substituted benzenes. The antifilarial properties of these synthetic anthraquinones were tested against microfilaria as well as adult male and female worms of B. malayi. The most active anthraquinone was K, which showed 100% mortality within 1, 5, and 3 days, respectively, against microfilaria and adult male and female worms at 5 ppm concentration. Albendazole, an oral drug currently used to treat parasitic infections, was used as a positive control. Methylated products of anthraquinones did not affect the microfilaria. Histological examination of treated adult female parasites showed most of the anthraquinones caused marked effects on intrauterine embryos.
Author List
Dhananjeyan MR, Milev YP, Kron MA, Nair MGAuthor
Michael Kron MD Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnthraquinones
Brugia malayi
Embryo, Nonmammalian
Female
Filaricides
Humans
In Vitro Techniques
Larva
Male
Structure-Activity Relationship