RARISETENOLIDE, EPOXYRARISETENOLIDE, AND EPIRARISETENOLIDE, NEW-SKELETON SESQUITERPENE LACTONES AS TAXONOMIC MARKERS AND DEFENSIVE AGENTS OF THE MARINE CILIATED MORPHOSPECIES EUPLOTES RARISETA

Rarisetenolide (3) and epoxyrarisetenolide (4), new-skeleton alpha,bet a-conjugated sesquiterpene lactones, were isolated from various strain s of the unicellular ciliated protist Euplotes rariseta collected from marine coasts widely far apart from each other: northern and southern Australia, southern Brazil, and Canary Islands. A strain of E. rarise ta from New Zealand gave epirarisetenolide (5) instead, revealing a su btle variability in secondary metabolism for this ciliated morphospeci es. Nonetheless, these metabolites - which are the first non-aldehydic terpenoids so far isolated from ciliates - represent a unique whole t hat constitutes a reliable taxonomic tool at the morphospecies level. Epirarisetenolide (5) and rarisetenolide (3), in this order, showed hi gher toxicity towards nonproductive ciliates than the chemically more reactive natural epoxide 4 and the semisynthetic aldehyde/protected-al dehyde forms 8/7a/7b. This inverse trend of biological vs. chemical ef fectiveness suggests that these cytotoxic agents interact noncovalentl y with membrane receptors.