Strains of the marine ciliate protist Euplotes crassus produce exclusive terpenoids called euplotins that play an ecological role. Among these derivatives, euplotin C is the main of four secondary metabolites isolated from cultures of this protozoon and represents the sesquiterpene taxonomic marker from E. crassus. Because different terpenoid metabolites of plant origin showed a certain antimicrobial activity, we assessed the compound euplotin C, purified by high-pressure liquid chromatography and solubilized in two solubility enhancers, against the protozoa Leishmania major and Leishmani infantum, the fungus Candida albicans, and nine strains of gram-positive and gram-negative microorganisms. An activity of euplotin C against Leishmania promastigotes was demonstrated (50% lethal doses were 4.6 or 8.1 g/ml depending on the agent used to solubilize the compound), while the effect was less evident on Candida and nearly absent on bacteria. A nonsignificant cytotoxicity (50% lethal dose, >200 g/ml) against the J774 cell line was observed. A leishmanicidal activity was also shown by the living, euplotin-producing cells of E. crassus cultured together with promastigotes; this activity increased with time from 10 min to 6 h of incubation. This study provides an initial rationale for the evaluation of euplotin C and other similar natural products as alternative or possibly synergistic compounds for current antiprotozoon chemotherapeutics.In recent years, several reports have been published on the scientifically confirmed antimicrobial activity of some natural products derived from plants (1,8,13,14,30,34,38,39) or of bioactive metabolites of microbial origin (26,32,33,35,40). Natural products showing effective action of pharmaceutical and medical relevance have also been recovered from marine organisms. Some bioactive antiviral, antitumor, antimicrobial, or generally cytotoxic compounds have been extracted from species of starfish and sponges. For example, extracts from the starfish Asterina pectifera are active against Aspergillus spp. and Cryptococcus neoformans (7), while various sponges exhibit antibacterial properties which are due to the presence of a metabolic product or to host microorganisms (12,25).Recently, four sesquiterpenes-euplotin A, euplotin B, euplotin C (EC), and their biogenetic precursor preuplotinhave been isolated from Euplotes crassus, a eukaryotic unicellular marine ciliate (16,19). All strains of this ciliate morphospecies (taxonomically described by microscopic, outwardly identifying features) produce the same compounds. Notably, euplotins, and in particular EC, are biosynthesized in relative large amounts, suggesting an important ecological role of this substance in the adaptive strategy of the organism. A similar terpenoid (udoteatrial hydrate) was isolated from Udotea flabellum (36), a tropical seaweed belonging to the phylum Chlorophyta that contributes to the structure of coral reefs. Indeed, it has been suggested that strong similarities in anthozoan metabolite biosynthesis reveal the ev...