JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Triterpenoids from Ganoderma gibbosum : A Class of Sensitizers of FLC-Resistant Candida albicans 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 ( 2 - 8 ) and gibbosic acids I-O ( 9 - 15 ), were isolated from the fruiting bodies of Ganoderma gibbosum , 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 C. albicans to FLC. Compounds 2 , 5 , 9 , 12 , 16 , 17 , and 21 exhibited strong antifungal activity against FLC-resistant C. albicans when combined with FLC, with MIC50 values ranging from 3.8 to 8.8 μg/mL.

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