Synthesis and Activity of Substituted Anthraquinones against a Human Filarial Parasite, Brugia malayi

Abstract

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.

Antiviral anthraquinones from the roots of Knoxia valerianoides

“…In addition to the three abovementioned new anthraquinones, nine known compounds were isolated from K. valerianoides. Through ESIMS analysis and comparisons with previously reported NMR data, their structures were confirmed as 1-methoxy-3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (4) (Ling et al, 2002), 3,6-dihydroxy-2-methoxymethyl-9,10-anthraquinone (5) (Chan et al, 2005), munjistin (6) (Itokawa et al, 1989), 1,2,3-trihydroxy-9,10-anthraquinone (7) (Dhananjeyan et al, 2005), arjunolic acid (8) (Shao et al, 1996), hyptatic acid A (9) (Yamagishi et al, 1988), hyptatic acid B (10) (Zhou et al, 1992), 2a,3b,24-trihydroxyurs-12-en-28-oic acid (11) (Li et al, 2014), and 2a,3b,23-trihydroxyurs-12-en-28-oic acid (12) (Adnyana et al, 2000). All of the isolates were evaluated their biological activities against Coxsackie virus B3 and influenza virus A/Hanfang/359/95.…”

A DFT computational study on the [3+2] cycloaddition between parent thionitrone and nitroethene

“…[6][7][8][9][10] The isothiazole ring is present in compounds with biological activity such as the pharmaceutical drugs ziprasidone and perospirone. 11,12 Subsequently, it should be noted, that the presence of nitro-group in the organic molecule generally stimulates additive functions of bioactivity. [13][14][15][16] Furthermore, nitro-group is an exceedingly attractive starting point for further transformation into many important organic groups and moieties.…”

Discovering New Classes of Brugia malayi Asparaginyl-tRNA Synthetase Inhibitors and Relating Specificity to Conformational Change

“…Planar, tricyclic scaffolds are potentially toxic because of their ability to intercalate DNA. Compounds sharing similar scaffolds have been shown to possess filaricidal activity against Brugia [70] and inhibit phosphodiesterase 4 (PDE4) [71]. Triazinylamine 4-(3-(4-amino-6-isopropenyl-1,3,5-triazin-2-yl)phenyl)-6-isopropenyl-1,3,5-triazin-2-ylamine (NCI code: NSC3636-24) has a symmetric structure with two substituted triazine rings connected by a phenyl group.…”