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Meroterpenoids from <i>Gongolaria abies-marina</i> against Kinetoplastids: <i>In Vitro</i> Activity and Programmed Cell Death Study
oleh: Desirée San Nicolás-Hernández, Rubén L. Rodríguez-Expósito, Atteneri López-Arencibia, Carlos J. Bethencourt-Estrella, Ines Sifaoui, Lizbeth Salazar-Villatoro, Maritza Omaña-Molina, José J. Fernández, Ana R. Díaz-Marrero, José E. Piñero, Jacob Lorenzo-Morales
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2023-03-01 |
Deskripsi
Leishmaniasis and Chagas disease affect millions of people worldwide. The available treatments against these parasitic diseases are limited and display multiple undesired effects. The brown alga belonging to the genus <i>Gongolaria</i> has been previously reported as a source of compounds with different biological activities. In a recent study from our group, <i>Gongolaria abies-marine</i> was proven to present antiamebic activity. Hence, this brown alga could be a promising source of interesting molecules for the development of new antiprotozoal drugs. In this study, four meroterpenoids were isolated and purified from a dichloromethane/ethyl acetate crude extract through a bioguided fractionation process targeting kinetoplastids. Moreover, the in vitro activity and toxicity were evaluated, and the induction of programmed cell death was checked in the most active and less toxic compounds, namely gongolarone B (<b>2</b>), 6<i>Z</i>-1′-methoxyamentadione (<b>3</b>) and 1′-methoxyamentadione (<b>4</b>). These meroterpenoids triggered mitochondrial malfunction, oxidative stress, chromatin condensation and alterations of the tubulin network. Furthermore, a transmission electron microscopy (TEM) image analysis showed that meroterpenoids (<b>2</b>–<b>4</b>) induced the formation of autophagy vacuoles and ER and Golgi complex disorganization. The obtained results demonstrated that the mechanisms of action at the cellular level of these compounds were able to induce autophagy as well as an apoptosis-like process in the treated parasites.