Bioactive polyketides and tryptophol alkaloids from the endophytic fungus Botryosphaeria dothidea LE-07 of Chinese tulip tree

Two new tetraketide-derived phenol rhamnosides [botryrhamnosides A (1) and B (2)] and a new rhamnosylated tryptophol alkaloid (botryrhamnoside C, 3), along with seven related known compounds (4–10) were isolated from the solid culture of Botryosphaeria dothidea LE-07, an endophytic fungus residing in the leaves of the rare medicinal plant Chinese tulip tree (Liriodendron chinense). Their structures with the absolute configurations were determined by a combination of spectroscopy methods, comparing specific rotations, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 are rare tetraketide-derived resorcinols incorporating a l-rhamnose moiety, while 3 represents the first example of rhamnose-bound tryptophol derivatives produced by microorganisms. These metabolites were evaluated in vitro for their antimicrobial and anti-neuroinflammation activities. The rhamnosylated derivatives 1–5 displayed potent antibacterial activity against Escherichia coli, with MIC values in the range of 8–16 μg/mL. Compound 2 attenuated neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 microglial cells, by decreasing the level of pro-inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6)] and down-regulating the mRNA expression of inducible nitric oxide synthase (iNOS). In addition, compound 8 exhibited remarkable inhibitory effect against the ATP-citrate lyase (ACL), an emerging drug target for hyperlipidemia and related glycolipid metabolic disorders, with an IC₅₀ value of 5.32 μM.