Triterpenoids from Ganoderma gibbosum: A Class of Sensitizers of FLC-Resistant Candida albicans to Fluconazole
By:Pu, Debing;Li, Xiaoning;Lin, Jing;Zhang, Ruihan;Luo, Ting;Wang, Yuan;Gao, Junbo;Zeb, Muhammad Aurang;Zhang, Xingjie;Li, Xiaoli;Wang, Ruirui;Xiao, Weilie
Journal of natural products
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 gamma-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 mug/mL.
Addresses:Key Laboratory of Medicinal Chemistry for Natural Resourceof Ministry of Education and Yunnan Province, School of Chemical Science and Technology ,Yunnan University, Kunming 650091 , People's Republic of China.
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences ,Yunnan University, Kunming 650091 , People's Republic of China.
School of Pharmaceutical Sciences ,Yunnan Universityof Chinese Medicine , Kunming 650500 , People's Republic of China.
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