Antimalarial 9‑Methoxystrobilurins, Oudemansins, and Related Polyketides from Cultures of Basidiomycete Favolaschia Species

• Published in: Journal of natural products (Washington, D.C.) Vol. 83; no. 4; pp. 905 - 917
• Main Authors: Kornsakulkarn, Jittra, Palasarn, Somporn, Choowong, Wilunda, Thongpanchang, Tienthong, Boonyuen, Nattawut, Choeyklin, Rattaket, Boonpratuang, Thitiya, Isaka, Masahiko, Thongpanchang, Chawanee
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 24-04-2020
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00647

Fourteen new compounds, oudemansins 1–4, oudemansinols 5–7, favolasins 8–10, favolasinin (12), polyketides 13–15, and (R,E)-2,4-dimethyl-5-phenyl-4-pentene-2,3-diol (16), together with nine known compounds were isolated from the basidiomycete fungus Favolaschia sp. BCC 18686. Two new compounds, favolasin E (11) and 9-oxostrobilurin E (17), were isolated from the closely related organism Favolaschia calocera BCC 36684 along with nine β-methoxyacrylate-type derivatives. Compounds in the class of oudemansins and strobilurins exhibited moderate to strong antimalarial activity with relatively low cytotoxicity against Vero cells (African green monkey kidney fibroblasts). Potent antimalarial activity was demonstrated for 9-methoxystrobilurins G, K, and E (IC50 values 0.061, 0.089, and 0.14 μM, respectively). The structure–activity relationships (SAR) for antimalarial activity is proposed on the basis of the activity of the new and several known β-methoxyacrylate derivatives in combination with the data from previously isolated compounds. Furthermore, several compounds showed specific cytotoxicity against NCI-187 cells (human small-cell lung cancer), although the SAR was different from that for antimalarial activity.