Triterpenoids from : A Class of Sensitizers of FLC-Resistant to Fluconazole

Fungal drug resistance is a major health threat, and reports of clinical resistance worldwide are becoming increasingly common. In a research program to discover new molecules to help overcome this problem, 14 new lanostane-type triterpenoids, gibbosicolids A-G (-) and gibbosic acids I-O (-), were isolated from the fruiting bodies of , along with seven known triterpenoid derivatives. These compounds featured high levels of oxidation, epimerization, and γ-lactonization. Structures were elucidated by comprehensive spectroscopic analyses and HRMS data. Absolute configurations were assigned based on quantum chemical calculations, including calculated chemical shift with DP4+ analysis, coupling constants, and electronic circular dichroism (ECD) methods. Results show that the calculated NMR with DP4+ analysis could not reliably establish the overall spatial configuration of molecules possessing independent and free-rotational stereoclusters. All these compounds significantly increased the sensitivity of fluconazole (FLC)-resistant to FLC. Compounds , , , , , , and exhibited strong antifungal activity against FLC-resistant when combined with FLC, with MIC values ranging from 3.8 to 8.8 μg/mL.