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新型白藜芦醇代用品抗阿尔茨海默病的设计、合成及体外药效学评价。

Design, Synthesis, and Invitro Pharmacological Evaluation of Novel Resveratrol Surrogate Molecules against Alzheimer's Disease.

机构信息

Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamilnadu, 603203, India.

Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia.

出版信息

Chem Biodivers. 2024 Sep;21(9):e202401430. doi: 10.1002/cbdv.202401430. Epub 2024 Aug 10.

Abstract

A series of resveratrol surrogate molecules were designed, synthesized and biologically evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) along with anti-oxidant activity as potential novel multifunctional agents against Alzheimer's disease (AD). Six novel compounds were synthesized by reacting (E)-4-(3,5-Dimethoxystyryl) aniline with benzaldehyde and some selected derivatives of benzaldehyde in the presence of ethanol and a few drops of glacial acetic acid which followed the general scheme involved in the formation of Schiff bases. The spectral analysis data including FT-IR, H-NMR, C-NMR, and Mass spectroscopy results were found to be in good agreement with the newly synthesized compounds (Resveratrol Surrogate Molecules 1-6). The synthesized compounds were evaluated for their dual cholinesterase inhibitory activities, cytotoxic effect, and anti-oxidant potential. The results showed that compound RSM5 showed potent inhibitory activity against AChE and BChE. In, addition the cytotoxicity of the compound RSM5 is less and found to be within the desirable limit indicating the potential safety of RSM5. Also, it possesses substantial anti-oxidant activity which qualifies RSM5 as an anti-AD agent. Taken together, these findings demonstrate that the molecule RSM5 had the most multifunctional properties and could be a promising lead molecule for the future development of drugs for Alzheimer's treatments.

摘要

设计、合成了一系列白藜芦醇类似物,并对其进行了乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)抑制活性及抗氧化活性的生物评价,以期发现具有多靶点作用的潜在阿尔茨海默病(AD)治疗药物。以(E)-4-(3,5-二甲氧基苯乙烯基)苯胺与苯甲醛及部分苯甲醛衍生物为原料,在乙醇和几滴冰醋酸存在下,通过一般的希夫碱形成反应合成了 6 种新型化合物。光谱分析数据(FT-IR、H-NMR、C-NMR 和质谱)与新合成的化合物(白藜芦醇类似物 1-6)吻合较好。对合成的化合物进行了双重胆碱酯酶抑制活性、细胞毒性和抗氧化活性评价。结果表明,化合物 RSM5 对 AChE 和 BChE 具有较强的抑制活性。此外,化合物 RSM5 的细胞毒性较小,在理想范围内,表明 RSM5 具有潜在的安全性。同时,它还具有较强的抗氧化活性,使 RSM5 成为一种具有抗 AD 作用的药物。综上所述,这些发现表明,RSM5 具有最多的多功能特性,可能成为未来开发治疗阿尔茨海默病药物的有前途的先导分子。

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