Abstract
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.
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Acknowledgments
The authors are grateful to Natural Products Research Nucleus and the School of Pharmaceutical Sciences of University of São Paulo for the access to their infrastructure.
Funding
The authors thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP/Brazil) for financial support (process number: 2012/02105-1, 2012/16168-5, and 2018/14150-8).
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GBP contributed to the conception of all experimental procedures, running the laboratory work, analysis of the data, and drafting the paper. LMP contributed to the execution of horseradish peroxidase activity assays, the analysis of data, and the elaboration of the manuscript. RAS contributed to the synthesis of the β-caryophyllene oxide sesquiterpene derivatives and elaborated the related material and methods, results, and discussion. PGAF contributed in standardization and execution of horseradish peroxidase activity assays. IFLG contributed to the execution of assays on trypomastigote forms of T. cruzi. GCC contributed to the synthesis planning and molecular structure elucidation of β-caryophyllene oxide sesquiterpene, revision, and critical reading of the manuscript. SA designed the study, supervised the laboratory work, and contributed to the critical reading of the manuscript. All the authors have read the final manuscript and approved the submission.
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Portapilla, G.B., Pereira, L.M., Soldi, R.A. et al. Activity of β-Caryophyllene Oxide Derivatives Against Trypanosoma cruzi, Mammalian Cells, and Horseradish Peroxidase. Rev. Bras. Farmacogn. 30, 824–831 (2020). https://doi.org/10.1007/s43450-020-00118-1
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DOI: https://doi.org/10.1007/s43450-020-00118-1