Optical Characteristics and Neuroprotective Properties of β-Dimethylaminoethylamide N-Benzoyl-DL-valine Iodmethylate and 1-(β-Diethylaminoethyl)-2-phenyl-4-benzylidene-5-imidazolone

IF 0.5 4区医学 Q4 NEUROSCIENCES

Neurochemical Journal Pub Date : 2024-01-30 DOI:10.1134/s1819712423040177

S. S. Mardanyan, L. G. Karapetyan, A. A. Antonyan, S. G. Sharoyan, H. V. Gasparyan, S. Buloyan, H. A. Harutyunyan, A. E. Pogosyan, L. Arshakyan, A. A. Hovhanesyan, V. O. Topuzyan

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Abstract

The water and DMSO solutions of two new synthesized compounds, β-dimethylaminoethylamidine N-benzoyl-DL-valineiodomethylate (TVA) and 1-(β-diethylaminoethyl)-2-phenyl-4-benzylidene-5-imidazolone (TVS), were characterized by optical absorbance and fluorescence properties. Earlier, the antiacetylcholinesterase and antibutyrylcholinesterase activities of these compounds have been shown. To prove the eligibility of their use against Alzheimer’s disease, the present study demonstrates the ability of the compounds to reduce the aggregation degree of commercial Aβ(1-42) amyloid peptide in vitro. From the concentration dependences, their IC₅₀ values were estimated in the deceleration of Aβ(1-42) aggregation (1.56 ± 0.3 mM for TVA and 1.8 ± 0.28 mM for TVS). The effective destabilization of the preformed aggregates of the peptide was registered with the IC₅₀ values of 0.54 ± 0.06 and 0.67 ± 0.2 mM, for TVA and TVS, respectively. Cell culture experiments have shown the effectiveness of the synthesized compounds in protection the rat hippocampal cells against cytotoxic action of Aβ(1-42) aggregates: during 7 days incubation, the number of neurospheres per microscopic field in the presence of the peptide aggregates fallen down to 34% of the intact cells, but 2 μg/mL TVA kept the cells on the level of the intact, and 5 μg/mL TVS—on the level of 77% of the intact. Subsequent developments based on these compounds will allow the researchers to create the preparations valid for pre-clinical studies with goal to introduce into medical practice as new remedies in prevention/treatment of Alzheimer’s disease.

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β-二甲基氨基乙酰胺 N-苯甲酰基-DL-缬氨酸碘甲酯和 1-(β-二乙基氨基乙基)-2-苯基-4-苄叉-5-咪唑啉酮的光学特征和神经保护特性

摘要利用吸光度和荧光特性对两种新合成化合物--β-二乙氨基乙脒 N-苯甲酰基-DL-缬氨碘甲基酸盐（TVA）和 1-（β-二乙氨基乙基）-2-苯基-4-亚苄基-5-咪唑啉酮（TVS）的水溶液和二甲基亚砜溶液进行了表征。早些时候，这些化合物的抗乙酰胆碱酯酶和抗丁酰胆碱酯酶活性已得到证实。为了证明这些化合物具有防治阿尔茨海默病的活性，本研究证明了这些化合物在体外降低商用 Aβ(1-42)淀粉样肽聚集度的能力。根据浓度相关性，估算出了它们在减缓 Aβ(1-42)聚集方面的 IC50 值（TVA 为 1.56 ± 0.3 mM，TVS 为 1.8 ± 0.28 mM）。TVA 和 TVS 的 IC50 值分别为 0.54 ± 0.06 毫摩尔和 0.67 ± 0.2 毫摩尔，有效地破坏了多肽预形成聚集体的稳定性。细胞培养实验表明，合成的化合物能有效保护大鼠海马细胞免受 Aβ(1-42)聚集体的细胞毒性作用：在 7 天的培养过程中，在多肽聚集体存在的情况下，每个显微视野中神经球的数量下降到完整细胞的 34%，但 2 μg/mL TVA 能使细胞保持在完整细胞的水平，而 5 μg/mL TVS 能使细胞保持在完整细胞的 77%。基于这些化合物的后续发展将使研究人员能够创造出有效的制剂，用于临床前研究，目标是将其引入医疗实践，作为预防/治疗阿尔茨海默病的新疗法。

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来源期刊

Neurochemical Journal 医学-神经科学

自引率

20.00%

发文量

审稿时长

>12 weeks

期刊介绍： Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.

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