Memnoniella is a fungal genus from which a wide range of diverse biologically active compounds have been isolated. A Memnoniella dichroa CF-080171 extract was identified to exhibit potent activity against Plasmodium falciparum 3D7 and Trypanosoma cruzi Tulahuen whole parasites in a high-throughput screening (HTS) campaign of microbial extracts from the Fundación MEDINA's collection. Bioassay-guided isolation of the active metabolites from this extract afforded eight new meroterpenoids of varying potencies, namely, memnobotrins C-E (1-3), a glycosylated isobenzofuranone (4), a tricyclic isobenzofuranone (5), a tetracyclic benzopyrane (6), a tetracyclic isobenzofuranone (7), and a pentacyclic isobenzofuranone (8). The structures of the isolated compounds were established by (+)-ESI-TOF high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Compounds 1, 2, and 4 exhibited potent antiparasitic activity against P. falciparum 3D7 (EC50 0.04-0.243 μM) and T. cruzi Tulahuen (EC50 0.266-1.37 μM) parasites, as well as cytotoxic activity against HepG2 tumoral liver cells (EC50 1.20-4.84 μM). The remaining compounds (3, 5-8) showed moderate or no activity against the above-mentioned parasites and cells.
Keywords: Chagas disease; HRMS; Memnoniella; NMR; Plasmodium falciparum; bioassay-guided isolation; malaria; meroterpenoids; natural products; parasites; tropical diseases; trypanosoma.