Gongolarones as antiamoeboid chemical scaffold
Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1′-methoxyamentadione (5) and 6Z-1′-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba.
Main Authors: | Rodríguez-Expósito, Rubén L., San Nicolás-Hernández, Desirée, Sifaoui, Ines, Cuadrado, Cristina, Salazar-Villatoro, Lizbeth, Reyes-Batlle, María, Hernández Daranas, Antonio, Omaña-Molina, Maritza, Fernández, José J., DIAZ MARRERO, ANA RAQUEL, Piñero, José E., Lorenzo-Morales, Jacob |
---|---|
Other Authors: | Ministerio de Ciencia e Innovación (España) |
Format: | artículo biblioteca |
Language: | English |
Published: |
Elsevier BV
2023-01-09
|
Subjects: | Acanthamoeba spp., gongolarones, meroterpenoid, gongolaria abies-marina, programmed cell death, autophagy, |
Online Access: | http://hdl.handle.net/10261/305393 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Similar Items
-
Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study
by: San Nicolás-Hernández, Desirée, et al.
Published: (2023-03-23) -
Amoebicidal effect of synthetic indoles against Acanthamoeba spp.: a study of cell death
by: Sifaoui, Ines, et al.
Published: (2024-02-27) -
Autophagy induced by purple pitanga (Eugenia uniflora L.) extract triggered a cooperative effect on inducing the hepatic stellate cell death.
by: DENARDIN, C. C., et al.
Published: (2017-01-26) -
Antiamoeboid activity of squamins C–F, cyclooctapeptides from Annona globifora
by: Rodríguez-Expósito, Rubén L., et al.
Published: (2021-12-09) -
Antifungal and antiprotozoal green amino acid-based rhamnolipids: Mode of action, antibiofilm efficiency and selective activity against resistant Candida spp. strains and Acanthamoeba castellanii
by: da Silva, Anderson, et al.
Published: (2020-09)