Zhang Jianpeng, Tan Ziling, Chen Yuchan, Li Chunan, Li Saini, Liu Hongxin, Zhang Weimin, Yan Hanjing
School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China.
Chem Biodivers. 2025 Feb;22(2):e202402114. doi: 10.1002/cbdv.202402114. Epub 2024 Nov 18.
Two undescribed letendrones A-B (1-2), along with three known compounds, ZL-6 (3), dankasterone B (4), and minimoidione B (5) were isolated from the Aquilaria-derived fungus Letendraea helminthicola A820. The structures of 1 and 2 were established by analysis of spectroscopes including 1D/2D NMR, IR, UV, and HRESIMS. Among them, the configuration of 1 was further confirmed by single-crystal X-ray diffraction. Letendrones A and B were the new phenalenyl derivatives with radical form that were firstly found in nature. In addition, bioactivity of these compounds was evaluated and compounds 3-5 exhibited inhibitory activity against LPS-induced NO production in macrophages with IC values of 4.64, 13.90, and 34.07 μM. Furthermore, potential targets of the new compounds were analyzed by molecular docking in silico. As a result, compound 1 showed high binding with predicted 5-HT receptor (▵G=-8.2 kcal/mol) potentially associated with depression disease, and compound 2 showed significant connection with phosphodiesterase 3 A (▵G=-9.4 kcal/mol) probably against cardiovascular disorders. Our findings firstly reported the high symmetry phenalenyl compounds from natural products which would provide a basis for further development and utilization of the secondary metabolites from the endophytic fungus Letendraea helminthicola A820.
从沉香属植物来源的真菌寄生勒特菌A820中分离出两种未描述的莱特酮A - B（1 - 2），以及三种已知化合物，ZL - 6（3）、丹卡甾酮B（4）和小穗酮B（5）。通过一维/二维核磁共振、红外光谱、紫外光谱和高分辨电喷雾电离质谱等光谱分析确定了1和2的结构。其中，1的构型通过单晶X射线衍射进一步得到证实。莱特酮A和B是首次在自然界中发现的具有自由基形式的新型菲并环戊二烯衍生物。此外，对这些化合物的生物活性进行了评估，化合物3 - 5对巨噬细胞中脂多糖诱导的一氧化氮产生具有抑制活性，IC值分别为4.64、13.90和34.07 μM。此外，通过计算机分子对接分析了新化合物的潜在靶点。结果显示，化合物1与预测的5 - 羟色胺受体具有高亲和力（ΔG = - 8.2 kcal/mol），可能与抑郁症相关；化合物2与磷酸二酯酶3A有显著结合（ΔG = - 9.4 kcal/mol），可能对抗心血管疾病。我们的研究首次报道了天然产物中的高对称性菲并环戊二烯化合物，这将为内生真菌寄生勒特菌A820次生代谢产物的进一步开发利用提供依据。
