Synthesis and activity of substituted anthraquinones against a human filarial parasite, Brugia malayi.
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.
Dhananjeyan
Mugunthu R
MR
Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, East Lansing, Michigan 48824, USA.
Milev
Youli P
YP
Kron
Michael A
MA
Nair
Muraleedharan G
MG
D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017178:Brugia malayi / Q000187:drug effects* / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005260:Female; D005369:Filaricides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007814:Larva / Q000187:drug effects; D008297:Male; D013329:Structure-Activity Relationship
C500616:1-methyl-2,3,8-trihydroxyanthraquinone; D000880:Anthraquinones; D005369:Filaricides