Novel tick glutathione transferase inhibitors as promising acaricidal compounds.

Autor: Ozelame KPC; Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Mattia MMC; Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Farmacociências, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil., Dedavid E Silva LA; Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Randall LM; Laboratorio de Moléculas Bioactivas, Departamento de Ciencias Biológicas, CENUR Litoral Norte, Universidad de la República, Paysandú, 60000, Uruguay., Corvo I; Laboratorio de Moléculas Bioactivas, Departamento de Ciencias Biológicas, CENUR Litoral Norte, Universidad de la República, Paysandú, 60000, Uruguay., Saporiti T; Laboratorio de Moléculas Bioactivas, Departamento de Ciencias Biológicas, CENUR Litoral Norte, Universidad de la República, Paysandú, 60000, Uruguay., Seixas A; Departamento de Farmacociências, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil., da Silva Vaz I Jr; Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: itabajara.vaz@ufrgs.br., Alvarez G; Laboratorio de Moléculas Bioactivas, Departamento de Ciencias Biológicas, CENUR Litoral Norte, Universidad de la República, Paysandú, 60000, Uruguay. Electronic address: guzmanalvarezlqo@gmail.com.
Jazyk: angličtina
Zdroj: Ticks and tick-borne diseases [Ticks Tick Borne Dis] 2022 Sep; Vol. 13 (5), pp. 101970. Date of Electronic Publication: 2022 May 23.
DOI: 10.1016/j.ttbdis.2022.101970
Abstrakt: Ticks are important ectoparasites with a worldwide distribution. The most commonly used method for tick control involves the use of acaricides. The main problem is that its indiscriminate use has led to the selection of resistant tick populations. Glutathione transferases (GSTs) are enzymes that play an important role in the detoxification of several types of compounds used in commercial tick control products. This work aims to find new bioactive molecules through in vitro assays with a panel of 160 molecules with putative inhibitory activity on the Rhipicephalus microplus GST enzyme (RmGST). Also, selected molecules were tested against GSTs from other tick species; Rhipicephalus decoloratus, Amblyomma variegatum, Rhipicephalus appendiculatus, and Haemaphysalis longicornis. The first screening on RmGST identified 30 compounds with the ability to modify the enzymatic activity of this enzyme. These compounds included different chemical families, like chalcones, diarylideneketones, flavone, thiazoles, thiourea, steroids, thiadiazines, indazoles, and hydrazine. The most potent compounds against RmGST belong to the diarylideneketones family with an inhibition concentration of 50% of activity (IC 50 ) between 7-50 μM. Interestingly, one of the most potent compounds was also an inhibitor of the GST from other tick species. Experiments with R. microplus adults and larvae showed toxicity at 150 μM, suggesting a potential acaricidal effect of these molecules.
(Copyright © 2022. Published by Elsevier GmbH.)
Databáze: MEDLINE
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