Antiparasitic Meroterpenoids Isolated from Memnoniella dichroa CF-080171.

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 (EC 50 0.04-0.243 μM) and T. cruzi Tulahuen (EC 50 0.266-1.37 μM) parasites, as well as cytotoxic activity against HepG2 tumoral liver cells (EC 50 1.20-4.84 μM). The remaining compounds ( 3 , 5 - 8 ) showed moderate or no activity against the above-mentioned parasites and cells.