Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the endophytic fungus Byssochlamys spectabilis IMM0002 and their biological activities

摘要

Abstract Bysspectin A ( 1 ), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C ( 2 and 3 ), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plant Edgeworthia chrysantha , together with a known octaketide, paecilocin A ( 4 ). Their structures were determined by HRMS, 1D and 2D NMR spectroscopic analysis. A plausible route for their biosynthetic pathway is proposed. Compounds 1 – 3 were tested for their antimicrobial activities. Only compound 3 was weakly active against Escherichia coli and Staphyloccocus aureus with MIC values of 32 and 64? μ g/mL, respectively. Further, the inhibitory effects on human carboxylesterases (hCE1, hCE2) of compounds 1 and 4 were evaluated. The results demonstrated that bysspectin A ( 1 ) was a novel and highly selective inhibitor against hCE2 with the IC 50 value of 2.01?μM. Docking simulation also demonstrated that active compound 1 created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen bonding, revealing its highly selective inhibition toward hCE2. Graphical abstract Display Omitted Highlights ? HPLC-PDA-MS HPLC-DAD-HRMS was applied to look for novel natural products with remarkable bioactivity. ? Isolation of a polyketide-derived octaketide dimer with a novel carbon skeleton. ? Bysspectin A ( 1 ) was a novel and highly selective inhibitor against hCE2. ? Bysspectin A ( 1 ) created interaction with the Ser-288 of hCE2 via hydrogen bonding.