Design, synthesis, and bio-evaluation of C1-aryl galantamine derivatives

IF 2.5 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia Pub Date : 2025-04-09 DOI:10.1016/j.fitote.2025.106535

Su-Mei Wang , Wan-Sheng Ji , Long-Jiang Chen , Lian-Hai Shan , Xiaohuan Li , Feng Gao , Jin-Bu Xu

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Abstract

For exploring the naturally-inspired anti-AD multifunctional molecules, a series of C1-aryl galantamine derivatives 4a-x were designed and synthesized. The cholinesterase inhibition activity and neuroprotection ability of 4a-x were evaluated. Among them, meta-tbutylbenzene derivative 4b (IC₅₀ = 0.12 ± 0.03 μM) and para-hydroxybenzene derivative 4h (IC₅₀ = 3.86 ± 0.82 μM) exhibited selective inhibition effect against EeAChE and EqBChE, respectively. Compound 4k containing meta-methylthio benzene group exhibited dual inhibitory activity against EeAChE (IC₅₀ = 0.47 ± 0.13 μM) and EqBChE (IC₅₀ = 2.98 ± 0.80 μM). Furthermore, the neuroprotection experiment revealed that eight synthesized derivatives had significant effect to protect SH-SY5Y cells from H₂O₂-induced damage at a concentration of 25 μM. Notably, the dual AChE and BChE inhibitor 4k also exhibited the good neuroprotective activity, which deserves to be further explored for developing potential multifunctional AD drug.

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C1 芳基加兰他敏衍生物的设计、合成和生物评估

为了探索从自然界获得灵感的抗逆转录酶多功能分子，研究人员设计并合成了一系列 C1-芳基加兰他敏衍生物 4a-x。对 4a-x 的胆碱酯酶抑制活性和神经保护能力进行了评估。其中，偏丁基苯衍生物 4b（IC50 = 0.12 ± 0.03 μM）和对羟基苯衍生物 4h（IC50 = 3.86 ± 0.82 μM）分别对 EeAChE 和 EqBChE 具有选择性抑制作用。含有偏甲硫基苯的化合物 4k 对 EeAChE（IC50 = 0.47 ± 0.13 μM）和 EqBChE（IC50 = 2.98 ± 0.80 μM）具有双重抑制活性。此外，神经保护实验显示，在 25 μM 的浓度下，合成的 8 种衍生物对保护 SH-SY5Y 细胞免受 H2O2 诱导的损伤有显著效果。值得注意的是，乙酰胆碱酯酶和乙酰胆碱酯酶双重抑制剂 4k 也表现出了良好的神经保护活性，值得进一步探索开发潜在的多功能抗抑郁药物。

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来源期刊

Fitoterapia 医学-药学

CiteScore

5.80

自引率

2.90%

发文量

198

审稿时长

1.5 months

期刊介绍： Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.