Discovery and Semisynthesis of Arthritacins A-J-Terpestacin-Derived Sesterterpenoids from the Plant Endophytic Fungus Arthrinium sp. HS66.

Arthrinium species are promising producers of terpenoids with diverse architectures and noteworthy pharmacological properties. In this work, ten undescribed terpestacin-type sesterterpenoids, arthritacins A-J (1-10), together with five known analogues (11-15), were obtained from the endophytic fungus Arthrinium sp. HS66 isolated from the stems of Isodon xerophilus. Their structures were established through comprehensive spectroscopic analysis, semisynthesis, and NMR calculations, further supported by DP4+ probability analysis. The semisynthetic studies further helped confirm the biosynthetically ambiguous configurations at C-11 and C-23 in terpestacin derivatives. All compounds were evaluated for cytotoxic activity against human neuroblastoma cells. Among them, compounds 1, 2, 4, 6, 7, 9, 12 and 13 showed moderate antiproliferative effects, with IC50 values ranging from 21.13 to 36.54 µM.