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

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 HRMS and NMR spectroscopic data. The absolute configuration was determined by chemical 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-κB. Compounds 1 and 3 strongly inhibited NF-κB with IC50 values of 7.1 and 1.5 μM, respectively.Fil: Li, Chun Shun. University of Hawai'i at Hilo; Estados UnidosFil: Sarotti, Ariel Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Huang, Peng. University of Hawai'i at Hilo; Estados Unidos. Anhui University of Chinese Medicine; ChinaFil: Dang, Uyen T.. Texas A&M University; Estados UnidosFil: Hurdle, Julian G.. Texas A&M University; Estados UnidosFil: Kondratyuk, Tamara P.. University of Hawai'i at Hilo; Estados UnidosFil: Pezzuto, J. M.. University of Hawai'i at Hilo; Estados Unidos. Arnold & Marie Schwartz College of Pharmacy and Health Sciences; Estados UnidosFil: Turkson, James Turkson. University of Hawai'i; Estados UnidosFil: Cao, Shugeng. University of Hawai'i at Hilo; Estados Unido