SCREENING OF COMPOUNDS FOR ANTIMICROSPORIDIAL ACTIVITY IN-VITRO

Relatively few effective compounds are available for treating microspo ridiosis in humans. In this study, several compounds were assayed for activity against Encephalitozoon intestinalis (Cali, Kotler et Orenste in, 1993) and Vittaforma corneae Shadduck, Meccoli, Davis et Font, 199 0 in vitro. Of the benzimidazoles tested, albendazole was most effecti ve and the MIC50 values were 8.0 ng/ml and 55.0 ng/ml for E. intestina lis and V. corneae, respectively. Fumagillin and its analogue, TNP-470 were nearly equally effective against both E. intestinalis and V, cor neae. The MIC50 values of fumagillin were 0.52 ng/ml and 0.81 ng/ml, a nd the MIC50, values of TNP-470 were 0.35 ng/ml and 0.38 ng/ml for E. intestinalis and V. corneae, respectively. In addition, 12 of 44 purin es and pteridines with putative tubulin binding activity that were syn thesized at Southern Research Institute (SRI), inhibited microsporidia l replication by more than 50% at concentrations that were not toxic t o the host cells. Several chitin synthesis/assembly inhibitors inhibit ed growth of the microsporidia in vitro but were toxic for the host ce lls making it difficult to interpret the results. One exception was lu fenuron, which caused no significant toxicity to the host cells and ex pressed approximate MIC50 values of 2.95 mu g/ml and 6.3 mu g/ml again st E, intestinalis and V. corneae, respectively. These results warrant further studies on albendazole, fumagillin, TNP-470, lufenuron, and t he selected SRI purines and pteridines for developing therapeutic stra tegies for microsporidiosis.