Isolation, Characterization, And Bioactivity Of Natural Products From Two Fungal Endophytes And One Medicinal Plant

Two strains of endophytic fungi, Diplodia cupressi (D. pinea f.sp. cupressi) and Diplodia pinea (Sphaeropsis sapinea), and one medicinal plant, Podocarpus imbricatus (Podocarpaceae) were chemically investigated. A total of 41 compounds including 11 new ones were obtained after separation and purification by column chromatography on silica gel, Rp-18 silica gel, and Sephadex LH-20 as well as preparative HPLC. The structures were determined on the basis of NMR, MS, UV, and IR spectroscopy. Some of the compounds were tested for their anti-proliferative activity on several tumor cell lines. The labdane-type diterpenoids from P. imbricatus showed anti-proliferative activity.Ten new compounds, diplocuprelides A-C (1-3), diplocupressins A-D (4-7), and cupressidones A-C (8-10) together with 14 known compounds, sphaeropsidins A-C (11-13), fusaproliferin (14),23,24,25,26,27-pentanorlanost-8-ene-3,22-diol (15), cis-3,4-dihydro-2,4,8-trihydroxynaphthalen-l-(2H)-one (16),trans-3,4-dihydro-2,4,8-trihydroxynaphthalen-1(2H)-one (17), sphaeropsidone (18), chlorosphaeropsidone (19), mevalonolactone (20),2-chloro-5-methoxy-1,4-hydroquinone (21),4-methoxy-resorcinol (22), orsellinic acid (23), and 2,3-dihydroxypropyl-9Z,12Z-octadecadi-enate (24) were obtained from the EtOAc extracts of D. cupressi. The structures of the compounds were established on the basis of extensive 1D and 2D NMR spectroscopic data analysis.Eight known compounds, stigmasta-7,22-diene-3β,5α,6β-triol (25), (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (26), hancinone C (27), isosclerone (28), scytalone (29), tetrahydro-4-hydroxy-6-pentyl-2H-pyran-2-one (30), flemingipanic acid (31), and 4-hydroxybenzaldehyde (32) were obtained from the extracts of D. pinea. Their structures were established on the basis of extensive spectroscopic analysis.One new diterpenoid, podoimbricatin A (33), as well as 8 known compounds, margoclin (34), agathic acid (35), abieta-8,11,13-triene-3β,6β,12-triol (36), abieta-8,11,13-triene-1β,3β,14-triol (37), amentoflavone (38), robustaflavone (39), 2,3-dihydrorobustaflavone (40), and 2,3-dihydrorobustaflavone-5-methyl ether (41) were obtained from the stems and leaves of P. imbricatus. Their structures were elucidated by spectroscopic analysis. Compounds 33 and 35 showed inhibitory effects against the A549 and NCI-H292 cancer cell lines.