Antiparasitic Activity of Sulfur- and Fluorine-Containing Bisphosphonates against Trypanosomatids and Apicomplexan Parasites

Abstract

Based on crystallographic data of the complexes 2-alkyl(amino)ethyl-1,1-bisphosphonates-<i>Trypanosoma cruzi</i> farnesyl diphosphate synthase, some linear 1,1-bisphosphonic acids and other closely related derivatives were designed, synthesized and biologically evaluated against <i>T. cruzi</i>, the responsible agent of Chagas disease and against <i>Toxoplasma gondii</i>, the etiologic agent of toxoplasmosis and also towards the target enzymes farnesyl pyrophosphate synthase of <i>T. cruzi</i> (<i>Tc</i>FPPS) and <i>T gondii</i> (<i>Tg</i>FPPS), respectively. The isoprenoid-containing 1,1-bisphosphonates exhibited modest antiparasitic activity, whereas the linear α-fluoro-2-alkyl(amino)ethyl-1,1-bisphosphonates were unexpectedly devoid of antiparasitic activity. In spite of not presenting efficient antiparasitic activity, these data turned out to be very important to establish a structural activity relationship.