State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, Yunnan Characteristic Plant Extraction Laboratory, School of Chemical Science and Technology, Yunnan University, Kunming 650500, People's Republic of China.
Bioorg Chem. 2023 Dec;141:106836. doi: 10.1016/j.bioorg.2023.106836. Epub 2023 Sep 9.
Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC value of 1.21 ± 0.16 μM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 μg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.
阿尔茨海默病（AD）和其他耐药菌引起的传染病对人类生命和全球健康构成了严重威胁。为了从药用植物中寻找人类乙酰胆碱酯酶（hAChE）抑制剂和抗菌剂，从 tropic Rhodomyrtus tomentosa 的叶子中分离得到了 16 种间苯三酚低聚物，包括两种新的间苯三酚单体（1a 和 1b）、四种新的间苯三酚二聚体（3a、3b、4b 和 5a）、六种新的间苯三酚三聚体（6a、6b、7a、7b、8a 和 8b）以及两种天然存在的间苯三酚单体（2a 和 2b），以及两种已知的同系物（4a 和 5b）。这些新分离物的结构和绝对构型通过全面分析其光谱数据（NMR 和 HRESIMS）、ECD 计算和单晶 X 射线衍射得到明确确定。结构上，3a/3b 具有罕见的 C-5'甲酰基，而 6a/6b 具有独特的 C-7'芳环。此外，7a/7b 和 8a/8b 是罕见的间苯三酚三聚体，具有双呋喃和 C-6'半缩酮基团。药理上，3a 和 3b 的混合物表现出最强的人乙酰胆碱酯酶（hAChE）抑制活性，IC 值为 1.21±0.16 μM。对 3a 和 3b 在 hAChE 结合部位的分子对接研究表明，与体外抑制作用具有良好的一致性。此外，3a 和 3b 的混合物对 MRSA（耐甲氧西林金黄色葡萄球菌）显示出最显著的抑制作用，MIC 和 MBC 值均为 0.50 μg/mL，扫描电子显微镜（SEM）研究表明它们可以破坏 MRSA 的生物膜结构。这些发现为进一步开发抗 AD 和抗菌剂提供了潜在的候选药物。
