葡萄糖偶联苯并[d]噻唑-噻唑烷-4-酮杂化物:多靶点抗阿尔茨海默病化合物的设计与合成

IF 4 3区 医学 Q2 CHEMISTRY, MEDICINAL
Nguyen Dinh Thanh*, Vu Ngoc Toan, Do Son Hai, Nguyen Minh Tri, Duong Ngoc Toan and Vu Minh Trang, 
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引用次数: 0

摘要

以相应的硫脲7a-k和溴乙酸乙酯为原料,在乙酸钠存在下,在氯仿中合成了一系列新的葡萄糖偶联2,3-噻唑-苯并[d]噻唑杂化化合物8a-k。抗阿尔茨海默病活性评价表明,部分化合物对AChE和BChE以及MAO-A和MAO-B酶具有明显的抑制活性。这些化合物对各酶的抑制顺序如下:8j >;8h(对AChE), 8k >;8b(对BChE), 8k >;8 g比;8f(对MAO-A)和8e >;8c(对MAO-B)。由于化合物8k对BChE和MAO-B酶分别具有有效或良好的活性,因此是一种感兴趣的抑制剂。化合物8j(抗AChE)和8k(抗BChE)具有竞争性,Ki常数分别为16.93 nM和17.09 nM。最有潜力的化合物8c、8j和8k对3T3细胞没有细胞毒性,具有很高的安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

d-Glucose-Conjugated Benzo[d]thiazole–thiazolidin-4-one Hybrids: Design and Synthesis as Multitarget Anti-Alzheimer Compounds

d-Glucose-Conjugated Benzo[d]thiazole–thiazolidin-4-one Hybrids: Design and Synthesis as Multitarget Anti-Alzheimer Compounds

A new series of d-glucose-conjugated 2,3-thiazoline–benzo[d]thiazole hybrid compounds 8ak were synthesized from reaction of the corresponding thioureas 7ak and ethyl bromoacetate in the presence of sodium acetate in chloroform. The evaluations for anti-Alzheimer activity showed that some compounds exhibited remarkable inhibitory activity against AChE and BChE as well as against MAO-A and MAO-B enzymes. The orders of inhibition for each enzyme of these compounds were as follows: 8j > 8h (against AChE), 8k > 8b (against BChE), 8k > 8g > 8f (against MAO-A), and 8e > 8c (against MAO-B). Compound 8k was an inhibitor of interest due to its potent or good activity against the two studied enzymes BChE and MAO-B, respectively. Compounds 8j (against AChE) and 8k (against (BChE) had a competitive type with Ki constants of 16.93 and 17.09 nM, respectively. The most potential compounds 8c, 8j, and 8k were not cytotoxic on 3T3 cells and had high levels of safety.

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来源期刊
ACS Medicinal Chemistry Letters
ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-
CiteScore
7.30
自引率
2.40%
发文量
328
审稿时长
1 months
期刊介绍: ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.
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