Paraverrucsins A–F, Antifeedant, and Antiphytopathogenic Polyketides from Rhizospheric Paraphaeosphaeria verruculosa and Induced Bioactivity Enhancement by Coculturing with Host Plant Dendrobium officinale

Six new polyketides named paraverrucsins A–F (1–6) with oxabicyclic and dioxatricyclic skeletons, together with eight known metabolites (7–14), were discovered and isolated from the fermentation medium of Paraphaeosphaeria verruculosa. Paraverrucsin A–C possessed a novel decarboxylated skeleton compared with that of trichocladinols. Their structures were elucidated by extensive spectral analysis and DP4+ calculations. Paraverrucsins B/C and D/E were isolated as a mixture for the mutarotation occurred at C-2. Paraverrucsins B/C, D/E, F/trichocladinol B, 8, and 9 displayed antifeedant activities against silkworm larvae, with antifeedant index percentages ranging from 62.5 to 93.0%, at a concentration of 50 μg/cm2. Among them, Paraverrucsins B/C and 9 had EC50 values at 13.9 and 18.2 μg/cm2. Most compounds showed antifungal activities against phytopathogenic fungi with minimum inhibitory concentration (MIC) values of 16–64 μg/mL. Coculture of P. verruculosa and host plant Dendrobium officinale leads to the enhancement of antifeedant and antiphytopathogenic activities. Compounds 1, 2/3, 4/5, 6/14 were tested for cytotoxicity against five human carcinoma cell lines, HL-60, A549, MCF-7, SW480, and SMMC-7721, while they exhibited selected cytotoxicity against SW480 with inhibition ratios of 32–38% at a concentration of 40 μM.