Activity of β-Caryophyllene Oxide Derivatives Against Trypanosoma cruzi, Mammalian Cells, and Horseradish Peroxidase

Plants are an important source of molecules that can control acute and chronic diseases. Malaria treatment represents a successful strategy in which an infection is controlled with compounds obtained from plants (for instance, artemisinin and quinine). Natural sources are an interesting reservoir of potential molecules that can act against protozoans, especially Trypanosoma cruzi. This parasite is the causative agent of Chagas disease, whose symptomatic chronic phase leads to cardiac and digestive complications. Despite the impacting complications of this disease, only two drugs are commercially available to treat it, nifurtimox and benznidazole. Thus, novel candidates for Trypanosoma cruzi control are desirable. Among the recent advances in this field, the diterpene copalic acid and the sesquiterpene β-caryophyllene oxide purified from copaiba plants have demonstrated antipathogenic properties, including trypanocidal activity. Here, we have studied some biological properties of copalic acid and performed several chemical modifications on β-caryophyllene oxide, which afforded six derivatives. These terpenes exerted different effects on amastigotes, epimastigotes, and trypomastigotes. In addition, they also inhibited the activity of horseradish peroxidase, a heme enzyme.