Ufisonitriles A and B, Antimalarial Isonitriles with Mitochondrial Function Inhibitory Activity Produced by...

Two novel antimalarials, named ufisonitriles A (1) and B (2), were isolated by bioassay-guided fractionation on mitochondrial function inhibitory activity using multidrug-sensitive budding yeast from the cultured broth of the Okinawan rare actinomycete Amycolatopsis sp. OK19-0009 strain. Their structures were comprehensively elucidated using HR-ESI-MS and 1D/2D NMR analyses and the modified Mosher's method. Structurally, 1 and 2 possess a novel skeleton with an isocyano group. In vitro antimalarial evaluation against Plasmodium falciparum strains revealed that 1 and 2 exhibited moderate activity with IC₅₀ values ranging from 28.6 to 1.12 μM. Furthermore, 1 and 2 reduced the malaria parasites by approximately 45% in vivo on intraperitoneal administration (30 mg/kg/day for 4 days) with no observed toxicity. We also provide a plausible biosynthesis pathway based on the genome sequence analysis.