Antifilarial activity of a synthetic marine alkaloid, aplysinopsin (CDRI Compound 92/138)

Abstract

CDRI Compound 92/138, a synthetic analogue of aplysinopsin, was evaluated in experimental filarial infections, Litomosoides carinii in cotton rats (Sigmodin hispidus) and Acanthocheilonema viteae in Mastomys coucha. The compound killed 63.8 and 90% of adult L. carinil and A. viteae at doses of 30 and 50 mg/kg (i.p.) respectively given for 5 days. By the oral route, at 100 mg/kg for 5 days the compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae, respectively. At 200 mg/kg administered orally on days 0, 10 and 25 post infection, it reduced establishment of adult A. viteae by 68.5%. We also found 43.7 and 37.8% effect in vivo respectively on L3 and L4 stages of A. viteae at a single dose of 250 mg/kg, p.o. The compound was active in vitro at 100 μg/ml concentration and caused a significant decline in MTT reduction and 14C-glucose uptake by adult filariids. Thus synthetic marine aplysinopsin could provide a new pharmacophore for the development of antifilarial agents.