Trypanocidal activity of flavonoids from Vitex simplicifolia

Trypanosomiasis is one of the public health problems, especially in tropical and subtropical regions and has been categorised by WHO as one of the neglected diseases. Therefore the search for novel, effective and safer drugs for the treatment of this disease continues ¹. A number of studies revealed that many plants are potential sources of novel trypanocidal compounds². We carried out in vitro and in vivo studies to determine the antitrypanosomal effects of the methanol extract of Vitex simplicifolia using Trypanosoma brucei brucei infected mice and Trypanosoma brucei rhodesiense. Successive extractions with hexane, dichloromethane (DCM), ethyl acetate, n-butanol and water coupled with activity guided fractionation proved the bioactivity of the DCM fraction. Further analysis of the DCM fraction by vacuum liquid chromatography, gel filtration using sephadex LH20, monitored with HPLC was followed by semi preparative HPLC to yield six pure compounds including 3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4 H-chromen-4-one (1), 3,5,7,8-tetrahydroxy-2-(4-methoxyphenyl) chroman-4-one (2), 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxy-4 H-chromen-4-one (3), 5-hydroxy-2-(4-hydroxyphenyl)-3,6,7-trimethoxy-4 H-chromen-4-one (4), 5-hydroxy– 2-(4-hydroxyphenyl)-3,7-dimethyoxy-4 H-chromen-4-one (5) and 2-(3,4-dimethoxyphenyl)-7-hydroxy-4 H-chromen-4-one (6). The structures of the isolated compounds were elucidated by 1- and 2D NMR spectroscopy, mass spectrometry as well as comparison with literature data. Compounds 4 – 6 exhibited significant trypanocidal activities ranging from 6.43 to 12.3 µg/ml and the cytotoxicity ranges from 1.58 to 6.64 µg/ml. This is the first report of trypanocidal effect of flavonoids from this plant.

References:

[1] Nwodo et al. Afr. J. Pharm. Res. Dev. 2012, 4(1) 35 – 40

[2] Hoet et al., Nat. Prod. Rep. 2004, 21, 353 – 364.