Asperaucystins A - L: Austocystins with immunosuppressive and cytotoxic activities from Aspergillus ustus NRRL 5856.

Our previous research on Aspergillus ustus NRRL 5856 led to the discovery of immunosuppressive austocystins, prompting further exploration of their structural diversity. Using "one strain many compounds" (OSMAC) strategy, the cultivation conditions were optimized, and various separation techniques were applied, resulting in the isolation of twelve unreported austocystins, namely asperaucystins A - L (1-12). The structures, including absolute configurations, were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction (SC-XRD), and electronic circular dichroism (ECD) calculations. Compounds 1-2 suppressed concanavalin A (ConA)-stimulated T cell proliferation and lipopolysaccharide (LPS)-stimulated B cell proliferation, with EC50 values of 8.1 and 7.1 μM, and 8.4 and 7.4 μM, respectively. Compounds 2, 4, 5, and 8 displayed cytotoxicity against the A427 cell line, with IC50 values of 12, 5.8, 7.3, and 3.4 μM, respectively. Compounds 2 and 4 also showed weak antimicrobial activity against Escherichia coli, each with an MIC of 64 μg/mL. These results highlight the significant immunosuppressive potential of austocystins, making them a promising class of agents for treating autoimmune diseases.