Peroxisome Proliferator Activated Receptor‐γ Agonistic Compounds from the Jellyfish‐Derived Fungus Cladosporium oxysporum

Abstract

In our search for peroxisome proliferator‐activated receptor (PPAR) agonists, five undescribed compounds, namely two acyclic diterpenes (1 and 2; cladopsol A and cladopsol B), two sesquiterpenes (3 and 4; cladopsol C and cladopsol D), and one C21‐ecdysteroid (5; cladopsol E), and 15 known compounds were isolated from the jellyfish‐derived fungus—Cladosporium oxysporum. The structures of the undescribed compounds were defined using UV, NMR, HRESIMS, and electronic circular dichroism (ECD) spectroscopy and a modified Mosher’s method. Luciferase reporter assay and docking analysis suggested that cladopsol B may function as a PPAR‐g partial agonist with a potential antidiabetic lead which may evade the side effects of full agonists. Moreover, cladopsol B stimulated glucose uptake in HepG2 cells with an efficacy comparable to that of rosiglitazone, but with less side effect induced by lipid accumulation in 3T3‐L1 cells. Therefore, cladopsol B could serve as a molecular skeleton in a study of advanced antidiabetic lead with less side effect.