4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia malayi.

A compound of the coumarin class, 4-methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one, was evaluated for antifilarial activity against the human filarial parasite, Brugia malayi (sub-periodic strain) in Mastomys coucha. The test compound brought about a 24.4% reduction in circulating microfilaremia on day 8 after initiation of treatment when administered by the peritoneal route at a dose of 50 mg/kg for 5 consecutive days. The compound also caused a 62.0% mortality in adult parasites. Apart from killing adult filariids, it also brought about sterilization of 81.8% of the surviving female B. malayi. An oral dose of 200 mg/kg for 5 consecutive days was less effective (35.5% adulticidal efficacy and 65.8% sterilization). In vitro, the compound killed adult B. malayi at 100 microM concentration and inhibited DNA topoisomerase II activity in the filarial parasite. Studies are in progress using the compound in combination with standard antifilarials as well as other active agents.