Ricerc@Sapienza

We discovered a series of azole antifungal compounds as effective antiprotozoal agents. They displayed promising inhibitory activities within the micromolar-submicromolar range against P. falciparum, L. donovani, and T. b. rhodesiense. Moreover, most of such compounds showed excellent nanomolar IC50against T. cruzi, showing also very low cytotoxicity. Discussion of structure-activity relationships and biological data for these compounds are provided against the different parasites. To assess the mechanism of action against T.

We have designed and synthesized a series of new imidazole-based compounds structurally related to an antiprotozoal agent with nanomolar activity which we identified recently. The new analogs possess micromolar activities against T. b. rhodesiense and L. donovani and nanomolar potency against P. falciparum. Most of the analogs displayed the IC50 within the low nanomolar range against T. cruzi, with very high selectivity towards the parasite. Discussion of structure-activity relationships and in vitro biological data for the new compounds are provided against a number of different protozoa.