Pseudeurglobosins A–F, six rearranged [11]-chaetoglobosins with immunosuppressive activities from Pseudeurotium bakeri P1-1-1

Abstract

Six rearranged [11]-chaetoglobosins (1–6) were isolated from an endophytic fungus Pseudeurotium bakeri P1-1-1. Pseudeurglobosin A (1) possesses a rare 5/6/5/4/6-fused pentacyclic ring system. Pseudeurglobosin B (2) has a C-14–O–C-18 bridged pentacyclic 5/6/6/5/6 core. Pseudeurglobosins C–E (3–5) represent the first examples of [11]-chaetoglobosins featuring a 5/6/6/7/5 ring system. Pseudeurglobosin F (6) features a unique 5/6/6 core. Compound 1 exhibited potent immunosuppressive activity against concanavalin A-induced T cell proliferation and lipopolysaccharide-induced B cell proliferation with IC₅₀ values of 6.0 ± 0.9 and 10.8 ± 0.3 μM, respectively. Further studies revealed that 1 induced apoptosis and inhibited cytokine secretion in activated T cells through the JAK2/PI3 K/Akt signaling pathway.