Isolation and In Vitro Activity of Sesquiterpene Lactones from Eremanthus crotonoides as SARS-CoV-2 Protease Inhibitors and Cytotoxic Agents

The Jurubatiba Sandbank National Park (PARNA Jurubatiba) is an ecological reserve characterized by harsh environmental conditions, including low rainfall, high sun exposure, and sandy soil. Among its native vegetation, <i>Eremanthus crotonoides</i> stands out for its richness in flavonoids, phenolic compounds, and sesquiterpene lactones. The objective of this study was to isolate and quantify sesquiterpene lactones from this species using ¹H NMR and to investigate their anti-SARS-CoV-2 potential and cytotoxicity against cancer cells. UPLC-(ESI)-MS/MS analyses enabled metabolite annotation, and semi-preparative HPLC-DAD allowed the isolation of centratherin and goyazensolide, which were identified by 1D and 2D NMR. In vitro assays showed that centratherin at 10 µM concentration reduced the viability of PC-3 and HCT-116 cancer cells by 100%, while goyazensolide had no noteworthy effects. Furthermore, enzymatic inhibition assays on SARS-CoV2 targets revealed that centratherin exhibited a lower apparent IC₅₀ of 12 µM against PL^pro, while goyazensolide was more active against 3CL^pro, with an IC₅₀ of 71 µM. Notably, the dichloromethane fraction demonstrated promising activity against both enzymes, with IC₅₀ values of 30 µM for PL^pro and 11 µM for 3CL^pro. This study reports, for the first time, the isolation of goyazensolide from <i>E. crotonoides</i> and highlights the potential of both sesquiterpene lactones as SARS-CoV-2 enzyme inhibitors. In contrast to centratherin, goyazensolide fortunately had almost no cytotoxic effects at inhibition concentration on the cells tested. This shows that anticancer and anti-SARS effects can be separated and should have different SARs, an important prerequisite for further development.