Synthesis and Screening of Substituted 1,4-Naphthoquinones (NPQs) as Antifilarial Agents

Eleven amino-substituted 1,4-naphthoquinones were synthesized via the reaction of 1,4-naphthoquinone with different primary and secondary mono- and diamines in the presence of dichloromethane ethanol (1:2) solvent at room temperature. All compounds were purified by flash column chromatography, characterized by TLC, HPLC, C-13-NMR, H-1-NMR, and FT-IR spectral analysis and were evaluated in vitro for antifilarial activity using adult bovine filarial worm Setaria digitata by assessing worm motility and MIT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction. Seven of the 11 compounds had macrofilaricidal activity with compounds 9 (2-[(1,3-dimethylbutyl) amino] naphthalene-1,4-dione) and 11 (2-(4-methylpiperazin-1-yl) naphthalene-1,4-dione) having maximum activity (ED50 values of 0.91 and 1.2 mu M, respectively, at 48 h). The effect of different substitutions on antifilarial activity is discussed. Drug Dev Res 71:188-196, 2010. (C) 2009 Wiley-Liss, Inc,