NF-KB inhibitors, unique gamma-pyranol-gamma-lactams with sulfide and sulfoxide moieties from Hawaiian plant Lycopodiella cernua derived fungus Paraphaeosphaeria neglecta FT462

HUANG, P.; KONDRATYUK, T. P. ; CAO, S.*; SAROTTI, A.M.; LI, C.; HURDLE, J.; DANG, U. T.; TURKSON, J.; PEZZUTO, J. M.

Scientific Reports - Nature

Nature

Año: 2017 vol. 7 p. 1 - 10

2045-2322

LC-UV/MS-based metabolomic analysis of the Hawaiian endophytic fungus Paraphaeosphaeria neglecta FT462 led to the identification of four unique mercaptolactated γ-pyranol?γ-lactams, paraphaeosphaerides E?H (1?4) together with one γ-lactone (5) and the methyl ester of compound 2 (11). The structures of the new compounds (1?5 and 11) were elucidated through the analysis of HRMSand NMR spectroscopic data. The absolute configuration was determined by hemical reactions with sodium borohydride, hydrogen peroxide, α- methoxy-α-trifluoromethyl)phenylacetyl chlorides (Mosher reagents), and DP4 + NMR calculations. All the compounds were tested against STAT3, A2780 and A2780cisR cancer cell lines, E. coli JW2496, and NF-kB. Compounds 1 and 3 strongly inhibited NF-kB with IC50 values of 7.1 and 1.5 μM, respectively.