Nidustrin A, cysteine-retained emestrin with a unique 18-membered macrocyclic lactone from the endophytic fungus Aspergillus nidulans

Bioorg Chem. 2024 Dec 28:155:108105. doi: 10.1016/j.bioorg.2024.108105. Online ahead of print.

Abstract

Nidustrin A (1), the first cysteine-retained emestrin featuring a unique sulfur-containing 18-membered macrocyclic lactone, along with four biogenetically related compounds (2-5), and one known analogue secoemestrin C (6), were isolated from the large-scale culture of Aspergillus nidulans, an endophytic fungus derived from the Whitmania pigra. Compounds 2 and 3 represent the second examples of noremestrin besides the previously reported noremestrin A, and the single crystal X-ray diffraction analysis of compound 2 provided solid evidence for the intriguing skeleton of noremestrin. Their structures were determined by extensive spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compounds 2-4 exhibited inhibitory activity against concanavalin A-induced T lymphocyte proliferation with IC50 values from 2.95 to 24.5 μM, respectively. Compound 4 could protect the liver from hepatocyte apoptosis in ConA-induced liver injury and showed moderate cytotoxic activities with IC50 values ranging from 3.26 to 15.70 μM.

Keywords: Aspergillus nidulans; Cytotoxic activities; Emestrin; Immunosuppressive activity; Structure elucidation.