Peniandrastins A–H: Andrastin-type meroterpenoids with immunosuppressive activity from a Penicillium sp.

Abstract

Eight unreported andrastin-type meroterpenoids, namely peniandrastins A–H (1–8), along with six known analogues (9–14), were isolated from the fermentation of a soil-derived fungus Penicillium sp.sb62. Their structures with absolute configurations were elucidated by detailed analyses of the spectroscopic data and single-crystal X-ray diffraction. Compounds 1–4 belong to a rare class of 21-nor-andrastin meroterpenoids, of which 1 bears a 10-hydroperoxyl group, and 2 and 3 feature a 6/6/6/5/5 and a 6/6/6/5/6 pentacyclic systems, respectively. Compounds 5–8 are C25 andrastin-type meroterpenoids, wherein 5 features an unprecedented cyclopentan-1-keton-3-hemiacetal moiety. Additionally, the absolute configuration of compound 9 was corroborated by single-crystal X-ray crystallography for the first time. All isolates were evaluated for their immunosuppressive activities. As a result, compounds 1, 3, 4, 7–9 and 12–14 inhibited concanavalin A-induced T cell proliferation with IC50 values ranging from 7.49 to 36.52 μM, and 1–4, 6–9 and 12–14 inhibited lipopolysaccharide-induced B cell proliferation with IC50 values ranging from 6.73 to 26.27 μM. The preliminary structure–activity relationships (SARs) of those isolates were also discussed.