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Mycotoxins from Fusarium proliferatum: new inhibitors of papain-like cysteine proteases

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Abstract

Papain-like cysteine proteases (PLCPs) in plants are essential to prevent phytopathogen invasion. In order to search for cysteine protease inhibitors and to investigate compounds that could be associated to pineapple Fusarium disease, a chemistry investigation was performed on Fusarium proliferatum isolated from Ananas comosus (pineapple) and cultivated in Czapek medium. From F. proliferatum extracts, nine secondary metabolites were isolated and characterized by nuclear magnetic resonance spectroscopy and mass spectrometry experiments: beauvericin (1), fusaric acid (2), N-ethyl-3-phenylacetamide (3), N-acetyltryptamine (4), cyclo(L-Val-L-Pro) cyclodipeptide (5), cyclo(L-Leu-L-Pro) cyclodipeptide (6), cyclo(L-Leu-L-Pro) diketopiperazine (7), 2,4-dihydroxypyrimidine (8), and 1H-indole-3-carbaldehyde (9). Compounds 1, 3, and 6 showed significant inhibition of papain, with IC50 values of 25.3 ± 1.9, 39.4 ± 2.5, and 7.4 ± 0.5 μM, respectively. Compound 1 also showed significant inhibition against human cathepsins V and B with IC50 of 46.0 ± 3.0 and 6.8 ± 0.7 μM, respectively. The inhibition of papain by mycotoxins (fusaric acid and beauvericin) may indicate a mechanism of Fusarium in the roles of infection process.

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Acknowledgments

The authors would like to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brasília, DF, Brazil) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brasília, DF, Brazil, Finance Code 001).

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Authors and Affiliations

  1. Department of Chemistry, Federal University of São Carlos, São Carlos, SP, 13565-905, Brazil

    Taynara Lopes Silva, João Batista Fernandes, Maria Fátima das Graças Fernandes da Silva & Paulo Cezar Vieira

  2. Department of Agronomy, Brasil University, Campus Descalvado, Descalvado, SP, 13565-905, Brazil

    Leonardo Toffano

  3. Special Academic Unit of Chemistry, Federal University of Goiás, Catalão regional, Catalão, GO, 75704-020, Brazil

    Lorena Ramos Freitas de Sousa

  4. School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14040-903, Brazil

    Paulo Cezar Vieira

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Silva, T.L., Toffano, L., Fernandes, J.B. et al. Mycotoxins from Fusarium proliferatum: new inhibitors of papain-like cysteine proteases. Braz J Microbiol 51, 1169–1175 (2020). https://doi.org/10.1007/s42770-020-00256-7

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