DNA topoisomerases of filarial parasites: effect of anti-filarial compounds

We have studied the filarial parasites Brugia malayi, Acanthocheilonema viteae and Setaria cervi adults and microfilariae of B. malayi and S. cervi and demonstrated the presence of ATP-independent (Topo I) and ATP-dependent (TOPO II) DNA topoisomerase activities. The enzyme activities were localized in the nuclear fraction of the parasites. Their distribution pattern differed between adults and microfilarial stages. In B. malayi adults and microfilariae, ATP-independent topoisomerase activity was significantly higher as compared to the ATP-requiring enzyme, while in S. cervi adults and microfilariae and ATP-dependent topoisomerase activity was significantly higher. In A. viteae adults both the enzymes were equally active. DNA topoisomerase inhibitors (nalidixic acid, novobiocin and ellipticine) exerted significant effects on ATP-independent and ATP-dependent topoisomerase activities of filarial parasites. The antifilarial compounds suramin and ivermectin proved to be strong inhibitors of the parasite enzymes. The inhibition by antifilarials and topoisomerase inhibitors suggests the potential of these enzymes as targets for the design of antifilarial agents. Med Sci Res 27:103-105 (C) 1999 Lippincott Williams & Wilkins.