Wang Jiamin, Li Rongfei, Lin Miaoping, Chen Chunmei, Qi Xin, Zhou Xuefeng, Liu Yonghong, Tan Yanhui, Luo Xiaowei
Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-efficient Utilization of Marine Traditional Chinese Medicine Resources, Guangxi, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
J Nat Prod. 2025 Jul 25;88(7):1671-1683. doi: 10.1021/acs.jnatprod.5c00425. Epub 2025 Jun 23.
Eight new prenylated indole alkaloids, brefeldindoles A-F (-), G (), and H (), together with 17 known analogues, were obtained from the Beibu Gulf mangrove-derived fungal strain GXIMD 02511. Their structures, including absolute configurations, were determined by analysis of spectroscopic data and electronic circular dichroism (ECD) calculations. Brefeldindoles A-F (-) are characterized as a rare class of indole-diterpenoid derivatives with uncommon 3-methyl-3-hydroxybutyl substituents in the benzene ring. Brefeldindole H () is the first example of an unprecedented 6/5/6/6/6/5-fused indole-diketopiperazine. Most alkaloids inhibited lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW264.7 macrophages at 20 μM. Preliminary structure-activity relationships are discussed. Compounds , , and suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without observed cytotoxicity in bone marrow macrophages (BMMs). Compound significantly inhibited NF-κB activation, leading to the suppression of nuclear translocation of NFATc1 and downregulation of the expression of osteoclast-related fusion protein DC-STAMP. Our findings indicated compound as a potential inhibitor of osteoclast differentiation for the treatment of bone destruction-related diseases.
从北部湾红树林来源的真菌菌株GXIMD 02511中获得了8个新的异戊烯基化吲哚生物碱，即布雷菲德吲哚A-F（-）、G（）和H（），以及17个已知类似物。通过光谱数据分析和电子圆二色性（ECD）计算确定了它们的结构，包括绝对构型。布雷菲德吲哚A-F（-）的特征是一类罕见的吲哚-二萜衍生物，其苯环上具有不常见的3-甲基-3-羟基丁基取代基。布雷菲德吲哚H（）是前所未有的6/5/6/6/6/5稠合吲哚-二酮哌嗪的首个实例。大多数生物碱在20 μM浓度下可抑制RAW264.7巨噬细胞中脂多糖（LPS）诱导的核因子κB（NF-κB）活化。讨论了初步的构效关系。化合物、和可抑制核因子κB受体活化剂配体（RANKL）诱导的破骨细胞分化，且在骨髓巨噬细胞（BMMs）中未观察到细胞毒性。化合物显著抑制NF-κB活化，导致活化T细胞核因子c1（NFATc1）的核转位受到抑制，并下调破骨细胞相关融合蛋白DC-STAMP的表达。我们的研究结果表明化合物是一种潜在的破骨细胞分化抑制剂，可用于治疗与骨破坏相关的疾病。
