Article
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential
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SCHIRMANN, Jéseka G. et al. In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphenyl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential. Scientific Reports, v. 17, p. 1-11, 2023.
2045-2322
Autor
Schirmann, Jéseka G.
Bortoleti, Bruna T. S.
Gonçalves, Manoela D.
Tomiotto‑Pellissier, Fernanda
Camargo, Priscila G.
Miranda‑Sapla, Milena M.
Lima, Camilo H. S.
Bispo, Marcelle L. F.
Costa, Idessania N.
Conchon‑Costa, Ivete
Pavanelli, Wander R.
Dekker, Robert F. H.
Barbosa‑Dekker, Aneli M.
Resumen
Available treatments for leishmaniasis have been widely used since the 1940s but come at a high cost, variable efcacy, high toxicity, and adverse side effects. 3,3′,5,5′-Tetramethoxy-biphenyl4,4′-diol (TMBP) was synthesized through laccase-catalysis of 2,6-dimethoxyphenol and displayed antioxidant and anticancer activity, and is considered a potential drug candidate. Thus, this study aimed to evaluate the anti-leishmanial efect of TMBP against promastigote and amastigote forms of Leishmania (L.) amazonensis and investigated the mechanisms involved in parasite death. TMBP treatment inhibited the proliferation (IC50 0.62–0.86 µM) and induced the death of promastigote forms by generating reactive oxygen species and mitochondrial dysfunction. In intracellular amastigotes, TMBP reduced the percentage of infected macrophages, being 62.7 times more selective to the parasite (CC50 53.93 µM). TMBP did not hemolyze sheep erythrocytes; indicative of low cytotoxicity. Additionally, molecular docking analysis on two enzyme targets of L. amazonensis: trypanothione reductase (TR) and leishmanolysin (Gp63), suggested that the hydroxyl group could be a pharmacophoric group due to its binding afnity by hydrogen bonds with residues at the active site of both enzymes. TMBP was more selective to the Gp63 target than TR. This is the frst report that TMBP is a promising compound to act as an anti-leishmanial agent.