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.
NMR, natural products, parasites, meroterpenoids, Trypanosoma, Plasmodium falciparum, Chagas disease, Malaria, bioassay-guided isolation, HRMS, Memnoniella, tropical diseases
NCBI PubMed ID: 36839814Publication DOI: 10.3390/pharmaceutics15020492Journal NLM ID: 101534003Publisher: Basel, Switzerland: MDPI
Correspondence: F.B. Annanag
; F. Reyes
Institutions: Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores de Andalucía, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 34, 18016 Granada, Spain, Instituto de Parasitología y Biomedicina ''López-Neyra'', Consejo Superior de Investigaciones Científicas (CSIC) Avda. del Conocimiento 17, Armilla, 18016 Granada, Spain
Methods: 13C NMR, 1H NMR, PCR, DNA techniques, biological assays, FTIR, UV, optical rotation measurement, RP-HPLC, ESI-TOF-MS, cytotoxicity assay, isolation
Found