Bibenzyl Derivatives from Radula voluta (An Ecuadorian Liverwort): Bioprospecting for Antiprotozoal Properties

Phytochemical investigation of <i>Radula voluta</i>, a liverwort species collected in the Ecuadorian Amazon, led to the isolation of four known bibenzyl derivatives: 2-prenyl-3,5-dihydroxy-bibenzyl (<b>1</b>), 2-geranyl-3,5-dihydroxybibenzyl (<b>2</b>), 2,2-dimethyl-5-phenethyl-2H-chromen-7-ol (<b>3</b>), and radulanin L (<b>4</b>). Structural elucidation was achieved through extensive NMR and MS analyses, supported by comparison with previously reported data. Compounds <b>1</b> and <b>4</b> are reported for the first time in <i>R. voluta</i>. The crude extract and isolated compounds were evaluated for their in vitro antiprotozoal activity against <i>Trypanosoma cruzi</i>, <i>Leishmania amazonensis</i>, <i>Leishmania donovani</i>, <i>Naegleria fowleri</i>, and <i>Acanthamoeba castellanii</i> Neff. Among the isolated compounds, bibenzyls <b>2</b> and <b>4</b> exhibited the most potent activity across multiple protozoan strains. Cytotoxicity was assessed against murine macrophages (J774A.1), obtaining moderate-low toxicities against compounds <b>1</b> and <b>3</b>. These findings highlight the pharmacological value of liverwort-derived bibenzyls and support further research on <i>R. voluta</i> as a promising source of antiparasitic leads.