Nguyen Dinh Thanh*, Vu Ngoc Toan, Do Son Hai, Nguyen Minh Tri, Duong Ngoc Toan and Vu Minh Trang,
{"title":"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","authors":"Nguyen Dinh Thanh*, Vu Ngoc Toan, Do Son Hai, Nguyen Minh Tri, Duong Ngoc Toan and Vu Minh Trang, ","doi":"10.1021/acsmedchemlett.5c0006410.1021/acsmedchemlett.5c00064","DOIUrl":null,"url":null,"abstract":"<p >A new series of <span>d</span>-glucose-conjugated 2,3-thiazoline–benzo[<i>d</i>]thiazole hybrid compounds <b>8a</b>–<b>k</b> were synthesized from reaction of the corresponding thioureas <b>7a</b>–<b>k</b> 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: <b>8j</b> > <b>8h</b> (against AChE), <b>8k</b> > <b>8b</b> (against BChE), <b>8k</b> > <b>8g</b> > <b>8f</b> (against MAO-A), and <b>8e</b> > <b>8c</b> (against MAO-B). Compound <b>8k</b> was an inhibitor of interest due to its potent or good activity against the two studied enzymes BChE and MAO-B, respectively. Compounds <b>8j</b> (against AChE) and <b>8k</b> (against (BChE) had a competitive type with <i>K</i><sub>i</sub> constants of 16.93 and 17.09 nM, respectively. The most potential compounds <b>8c</b>, <b>8j</b>, and <b>8k</b> were not cytotoxic on 3T3 cells and had high levels of safety.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1024–1030 1024–1030"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"d-Glucose-Conjugated Benzo[d]thiazole–thiazolidin-4-one Hybrids: Design and Synthesis as Multitarget Anti-Alzheimer Compounds\",\"authors\":\"Nguyen Dinh Thanh*, Vu Ngoc Toan, Do Son Hai, Nguyen Minh Tri, Duong Ngoc Toan and Vu Minh Trang, \",\"doi\":\"10.1021/acsmedchemlett.5c0006410.1021/acsmedchemlett.5c00064\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >A new series of <span>d</span>-glucose-conjugated 2,3-thiazoline–benzo[<i>d</i>]thiazole hybrid compounds <b>8a</b>–<b>k</b> were synthesized from reaction of the corresponding thioureas <b>7a</b>–<b>k</b> 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: <b>8j</b> > <b>8h</b> (against AChE), <b>8k</b> > <b>8b</b> (against BChE), <b>8k</b> > <b>8g</b> > <b>8f</b> (against MAO-A), and <b>8e</b> > <b>8c</b> (against MAO-B). Compound <b>8k</b> was an inhibitor of interest due to its potent or good activity against the two studied enzymes BChE and MAO-B, respectively. Compounds <b>8j</b> (against AChE) and <b>8k</b> (against (BChE) had a competitive type with <i>K</i><sub>i</sub> constants of 16.93 and 17.09 nM, respectively. The most potential compounds <b>8c</b>, <b>8j</b>, and <b>8k</b> were not cytotoxic on 3T3 cells and had high levels of safety.</p>\",\"PeriodicalId\":20,\"journal\":{\"name\":\"ACS Medicinal Chemistry Letters\",\"volume\":\"16 6\",\"pages\":\"1024–1030 1024–1030\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-05-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Medicinal Chemistry Letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00064\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00064","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
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 8a–k were synthesized from reaction of the corresponding thioureas 7a–k 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.
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.