2. Academic Validation
  3. Anonaine from Annona crassiflora inhibits glutathione S-transferase and improves cypermethrin activity on Rhipicephalus (Boophilus) microplus (Canestrini, 1887)

Anonaine from Annona crassiflora inhibits glutathione S-transferase and improves cypermethrin activity on Rhipicephalus (Boophilus) microplus (Canestrini, 1887)

  • Exp Parasitol. 2022 Dec;243:108398. doi: 10.1016/j.exppara.2022.108398.
Wallyson André Dos Santos Bezerra 1,  Caio Pavão Tavares 2,  Cláudia Quintino da Rocha 3,  Itabajara da Silva Vaz Junior 4,  Paul A M Michels 5,  Livio Martins Costa Junior 2,  Alexandra Martins Dos Santos Soares 6
Affiliations

Affiliations

  • 1 Laboratório de Bioquímica Vegetal, Departamento de Engenharia Química, Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia, Universidade Federal do Maranhão, São Luís, MA, Brazil.
  • 2 Laboratório de Controle de Parasitos, Departamento de Patologia, Universidade Federal do Maranhão, São Luís, MA, Brazil.
  • 3 Laboratório de Química de Produtos Naturais, Departamento de Química, Universidade Federal do Maranhão, São Luís, MA, Brazil.
  • 4 Faculdade de Veterinária e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • 5 Centre for Immunity, Infection and Evolution and Centre for Translational and Chemical Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
  • 6 Laboratório de Bioquímica Vegetal, Departamento de Engenharia Química, Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia, Universidade Federal do Maranhão, São Luís, MA, Brazil. Electronic address: [email protected].
PMID: 36228702 DOI: 10.1016/j.exppara.2022.108398
Abstract

Rhipicephalus (Boophilus) microplus (Canestrini, 1887) is one of the most important ectoparasites of cattle, causing severe economic losses in tropical and subtropical regions of the world. The selection of resistance to the most commonly used commercial acaricides has stimulated the search for new products for tick control. The identification and development of drugs that inhibit key tick enzymes, such as glutathione S-transferase (GST), is a rational approach that has already been applied to other parasites than ticks. In this context, Alkaloids such as anonaine display several biological activities, including an acaricidal effect. This study aimed to assess the specific inhibition of the R. microplus GST by anonaine, and analyze the effect on ticks when anonaine is combined with cypermethrin. For this purpose, a molecular docking analysis was performed using an R. microplus GST three-dimensional structure model with anonaine and compared with a human GST-anonaine complex. The absorption, distribution, metabolism, excretion, and toxicity properties of anonaine were also predicted. Then, for in vitro analyses, anonaine was isolated from Annona crassiflora (Martius, 1841) leaves. The inhibition of purified recombinant R. microplus GST (rRmGST) by anonaine and the effect of this alkaloid on cypermethrin efficacy towards R. microplus were assessed. Anonaine has a higher affinity to the tick Enzyme than to the human Enzyme in silico and has moderate toxicity, being able to inhibit, in vitro, rRmGST up to 37.5% in a dose-dependent manner. Although anonaine alone has no activity against R. microplus, it increased the cypermethrin effect on larvae, reducing the LC50 from 44 to 22 μg/mL. In conclusion, anonaine is a natural compound that can increase the effect of cypermethrin against R. microplus.

Keywords

GST inhibition; Plant alkaloid; Pyrethroid; Tick.

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