In silico and In vitro Assessment of Dimeric Flavonoids (Brachydins) on Rhipicephalus microplus Glutathione S-transferase.

Autor: Dos Santos Bezerra WA; Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia - Bionorte, Universidade Federal do Maranhão, São Luís, MA, Brazil., Tavares CP; Laboratório de Controle de Parasitos, Departamento de Patologia, Universidade Federal do Maranhão, São Luís, MA, Brazil., Lima VAS; Laboratório de Química de Produtos Naturais, Departamento de Química, Universidade Federal do Maranhão, São Luís, MA, Brazil., da Rocha CQ; Laboratório de Química de Produtos Naturais, Departamento de Química, Universidade Federal do Maranhão, São Luís, MA, Brazil., da Silva Vaz Junior I; Faculdade de Veterinária, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Michels PAM; School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Costa Junior LM; Laboratório de Química de Produtos Naturais, Departamento de Química, Universidade Federal do Maranhão, São Luís, MA, Brazil., Dos Santos Soares AM; Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia - Bionorte, Universidade Federal do Maranhão, São Luís, MA, Brazil.; Laboratório de Bioquímica Vegetal, Departamento de Engenharia Química, Universidade Federal do Maranhão, São Luís, MA, Brazil.
Jazyk: angličtina
Zdroj: Medicinal chemistry (Shariqah (United Arab Emirates)) [Med Chem] 2024; Vol. 20 (9), pp. 912-919.
DOI: 10.2174/0115734064298481240517072216
Abstrakt: Introduction: Rhipicephalus microplus , an important cattle ectoparasite, is responsible for a substantial negative impact on the economy due to productivity loss. The emergence of resistance to widely used commercial acaricides has sparked efforts to explore alternative products for tick control.
Methods: To address this challenge, innovative solutions targeting essential tick enzymes, like glutathione S-transferase (GST), have gained attention. Dimeric flavonoids, particularly brachydins (BRAs), have demonstrated various biological activities, including antiparasitic effects. The objectives of this study were to isolate four dimeric flavonoids from Fridericia platyphylla roots and to evaluate their potential as inhibitors of R. microplus GST.
Results: In vitro assays confirmed the inhibition of R. microplus GST by BRA-G, BRA-I, BRA-J, and BRA-K with IC 50 values of 0.075, 0.079, 0.075, and 0.058 mg/mL, respectively, with minimal hemolytic effects. Molecular docking of BRA-G, BRA-I, BRA-J, and BRA-K in a threedimensional model of R. microplus GST revealed predicted interactions with MolDock Scores of - 142.537, -126.831, -108.571, and -123.041, respectively. Both in silico and in vitro analyses show that brachydins are potential inhibitors of R. microplus GST.
Conclusion: The findings of this study deepen our understanding of GST inhibition in ticks, affirming its viability as a drug target. This knowledge contributes to the advancement of treatment modalities and strategies for improved tick control.
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Databáze: MEDLINE
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