＜正＞拳距瓜叶乌头（Aconitum hemsleyanum var.circinatum）是毛茛科（Ramunculaceae）乌头属（Aconitum）植物,为瓜叶乌头变种（Aconitum hemsleyanum Pritz）。广泛分布于我国四川西部、云南西北部、贵州西部等地1。其块根民间药用于治跌打损伤,关节疼痛2。瓜叶乌头因分布较广,形态性状相似,故有学者认为可其变种进行归并3。因此,对拳距瓜叶乌头进行系统的植物化学成分研究可为其分类学提供依据。本研究综合利用正反相柱层析、薄层层析、HPLC、重结晶等方法,从拳距瓜叶乌头干燥根块的乙醇提取物中分离得到14个二萜生物碱类化合物,

Two new lappaconitine-type C-18-diterpenoid alkaloids, named as leucostosines C (1) and D (2), together with six known compounds (3-8), were isolated from the roots of Aconitum leucostomum Worosch. Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, NMR spectra and X-ray experiments. Leucostosine C is the first diterpenoid alkaloid bearing the 7-amino group. The isolated compounds were tested for the acetylcholinesterase (AChE) inhibitory effect and neuroprotective activity, none of them showed significant activities.

Breast cancer is still one of the most common malignancies worldwide and remains a major clinical challenge. We previously reported that the anthelmintic drug flubendazole induced autophagy and apoptosis via upregulation of eva-1 homolog A (EVA1A) in triple-negative breast cancer (TNBC) and was repurposed as a novel anti-tumor agent. However, the detailed underlying mechanisms remain unclear and need further investigation. Here, we found that flubendazole impairs the permeability of the mitochondrial outer membrane and mitochondrial function in breast cancer. Meanwhile, flubendazole increased dynamin-related protein (DRP1) expression, leading to the accumulation of PTEN induced putative kinase 1 (PINK1) and subsequent mitochondrial translocation of Parkin, thereby promoting excessive mitophagy. The resultant excessive mitophagy contributed to mitochondrial damage and dysfunction induced by flubendazole, thus inhibiting breast cancer cells proliferation and migration. Moreover, we demonstrated that excessive DRP1-mediated mitophagy played a critical role in response to the anti-tumor effects of EVA1A in breast cancer. Taken together, our results provide new insights into the molecular mechanisms in relation to the anti-tumor activities of flubendazole, and may be conducive to its rational use in potential clinical applications.

Seven previously undescribed diterpenoid alkaloids, eight reaction products and thirteen known compounds were isolated from the whole plant of Delphinium grandiflorum L. (Ranunculaceae). Grandiflonines A and B have an unprecedented C-20-diterpenoid alkaloid skeleton, which features inversion of the configuration of C-18. Their structures were determined by comprehensive analyses of spectroscopic data, X-ray diffraction and Mosher's method. The probable biosynthetic pathway of grandiflonine A was discussed. Additionally, the analgesic activity and anti-inflammatory activity by inhibition of NO production were evaluated. Among them, deoxylappaconitine (ED50 = 0.35 mg/kg, TI = 46.22) showed significant analgesic activity that was superior to the reference drug lappaconitine (ED50 = 3.5 mg/kg, TI = 3.34).

Palladium/BuAd(2)P efficiently catalyzed the direct alpha-arylation of ketone in the anti-Alzheimer's disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridinyl analogue (12) shows significantly lower toxicity compared to donepezil and remarkable neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. Docking results of compound 12 also interpreted the possible mechanism of the selective inhibition between AChE and butyrylcholinesterase (BuChE).

该文对藏族药工布乌头Aconitum kongboense块根进行了系统的化学成分研究。运用硅胶柱色谱、反相硅胶柱色谱、碱性氧化铝柱色谱等分离纯化方法,从工布乌头95%甲醇提取液中分离鉴定25个二萜生物碱,包括1个新的乌头碱型C19-二萜生物碱,命

A new series of N-aryltacrine derivatives were designed and synthesized as cholinesterase inhibitors by the latestage modification of tacrine, using the palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. In vitro inhibition assay against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) demonstrated that most of the synthesized compounds had potent AChE inhibitory activity with negative inhibition of BuChE. Among them, N-(4-(trifluoromethyl)phenyl)tacrine (3g) and N-(4-methoxypyridin-2-yl)-tacrine (3o) showed the most potent activity against AChE (IC50 values of 1.77 and 1.48 mu M, respectively). The anti-AChE activity of 3g and 3o was 3.5 times more than that of tacrine (IC50 value of 5.16 mu M). Compound 3o also displayed anti-BuChE activity with an IC50 value of 19.00 mu M. Cell-based assays against HepG(2) and SH-SY5Y cell lines revealed that 3o had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. The advantages including synthetic accessibility, high potency, low toxicity, and adjunctive neuroprotective activity make compound 3o a new promising multifunctional candidate for the treatment of Alzheimer's disease.

Five new aconitine-type C-19-diterpenoid alkaloids, apetalrines A-E (1-5), were isolated from Aconitum apetalum. Their structures were determined by analysis of 1D and 2D NMR, IR, and HRESIMS data. Semisynthesis of apetalrine B (2) from its parent compound aconorine was achieved to confirm the structure proposed. Twenty derivatives of 2 (11a-11l, 12a, 12b, 12d, 12e, 12j, 12k, 12m, 12n) were synthesized via a unified approach relying on simple coupling reactions. The evaluation of neuroprotective effects of compounds (1-5, 11b, 11c, 11f-11i, 112a, 12b, 12d, 12e, 12k, 12m, 12n) with low cytotoxicity revealed compound 2 to exhibit good neuroprotective effects in H2O2-treated SH-SYSY cells at a concentration of 50 mu M. A series of studies using flow cytometry, staining, and Western blotting on 2 indicated that its neuroprotective effects may arise from inhibiting cell apoptosis.