三萜类化合物从：一类对氟康唑耐药的 FLC 的敏化剂。
Triterpenoids from : A Class of Sensitizers of FLC-Resistant to Fluconazole.
机构信息
Key Laboratory of Medicinal Chemistry for Natural Resource of 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.
出版信息
J Nat Prod. 2019 Aug 23;82(8):2067-2077. doi: 10.1021/acs.jnatprod.9b00148. Epub 2019 Jul 16.
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.
真菌药物耐药性是一个主要的健康威胁，全球范围内临床耐药的报告越来越常见。在一个旨在发现新分子以帮助克服这一问题的研究计划中，从 中分离出了 14 种新的羊毛甾烷型三萜类化合物，即 gibbosicolids A-G(-)和 gibbosic acids I-O(-)，以及 7 种已知的三萜类衍生物。这些化合物具有高水平的氧化、差向异构化和γ-内酯化。通过全面的光谱分析和高分辨率质谱（HRMS）数据确定了结构。根据量子化学计算，包括 DP4+分析计算的化学位移、偶合常数和电子圆二色性（ECD）方法，确定了绝对构型。结果表明，DP4+分析计算的 NMR 无法可靠地确定具有独立和自由旋转立体簇的分子的整体空间构型。所有这些化合物均显著提高了氟康唑（FLC）耐药 的 FLC 敏感性。化合物 、 、 、 、 、和 与 FLC 联合使用时对 FLC 耐药 表现出强烈的抗真菌活性，MIC 值范围为 3.8 至 8.8μg/mL。
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