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Lymphatic filariasis is a disfiguring disease caused by parasitic worms that destroy the human lymphatic system leading to substantial morbidity. The current drug of choice for the treatment of filariasis is diethylcarbamazine and ivermectin with albendazole which are only effective against the microfilaria, leaving the adult worm unaffected, requiring the development of "adulticidal drugs." Thirty amino substituted 2-hydroxy/5-hydroxy/2-methyl-1,4-naphthoquinones were synthesized via the reac- tion of 2-hydroxy/5-hydroxy/2-methyl-1,4-naphthoquinones with different primary and secondary amines. Compounds 1-30 were evaluated for in vitro antifilarial activity against the adult bovine filarial worm Setaria digitata as assessed by worm motility and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) reduction assays. The mutagenecity, tumerogenecity, irritantancy, repro- ductive toxicity, drug score, druglike, and cLogP properties were calculated using OSIRIS property predictor. Ten compounds showed macrofilaricidal activity with ED50 values ranging between 0.086 and 7.6 mM. Taking into account the biological effects and the promising drug-like profiles of these com- pounds, these represent valid leads for the development of antifilarial agents against adult filarial worm. Drug Dev Res 74 : 216-226, 2013. © 2013 Wiley Periodicals, Inc.

The crude extract of the stembark of Streblus asper, a traditionally used medicinal plant of India, revealed significant macrofilaricidal activity against Litomosoides carinii and Brugia malayi in rodents. The study revealed two cardiac glycosides, K029 (asperoside) and K030 (strebloside) of the extract to be responsible for antifilarial activity. Of the two glycosides, the more effective macrofilaricide was K029 which was active at 50 mg/kg orally against L. carinii (>90%), B. malayi (>70%), and Acanthocheilonema viteae (>70%) in their respective hosts. The glycosides were also active in vitro against all the three filarial species. Significantly weak activity was detected in glycon and aglycon portions of the parent glycosides (K029 and K030). Several cardiac glycosides of other origins did not show any comparable antifilarial efficacy. The aglycosidic portion of the extract, however, showed poor adulticidal activity (44.5% activity at 1 g/kg against L. carinii). The present finding, thus, opens up the possibility of generating new leads in the development of novel macrofilaricides. © 1992 Wiley-Liss, Inc.