Polyamines: agents with macrofilaricidal activity

There is a need for effective macrofilaricidal drugs. The polyamine metabol ism of filarial worms has been recognized as a possible target for effectiv e drug action. In an attempt to identify agents that might provide leads in developing an effective macrofilaricide, 78 polyamine compounds were selec ted from among > 250 000 structures that have been amassed by the Waiter Re ed Army Institute of Research, in the U.S.A. These thousands of agents have been chosen principally for drug-development programmes for other parasiti c diseases. The 78 prospective drugs selected were evaluated for their macr ofilaricidal activity against Brugia pahangi and Acanthocheilonema viteae, in male Mongolian jirds (Meriones unguiculatus). The animal models using th ese two parasites were designed to mimic, in so far as possible, human lymp hatic filariasis and onchocerciasis, respectively. Thirteen of the compound s were found to be active although none of these has been previously report ed to be macrofilaricidal. Two were suppressive for B. pahangi and 11 for A . viteae. These active agents may represent a nucleus around which highly e ffective drugs can be synthesised.