{"title":"靛红类化合物的分子杂交、合成、体外α-葡萄糖苷酶抑制作用、体内抗糖尿病活性和计算研究","authors":"","doi":"10.1016/j.bioorg.2024.107783","DOIUrl":null,"url":null,"abstract":"<div><p>In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both <em>in vitro</em> and <em>in vivo</em> assays. The tested compounds 7a-7j demonstrated <em>In vitro</em> inhibitory potential against <em>α-glucosidase</em>, as indicated by their IC<sub>50</sub> values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC<sub>50</sub> value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for <em>in vivo</em> evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both <em>in vitro</em> and <em>in vivo</em>, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the <em>α-glucosidase</em> enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.</p></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Molecular hybridization, synthesis, in vitro α-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds\",\"authors\":\"\",\"doi\":\"10.1016/j.bioorg.2024.107783\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both <em>in vitro</em> and <em>in vivo</em> assays. The tested compounds 7a-7j demonstrated <em>In vitro</em> inhibitory potential against <em>α-glucosidase</em>, as indicated by their IC<sub>50</sub> values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC<sub>50</sub> value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for <em>in vivo</em> evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both <em>in vitro</em> and <em>in vivo</em>, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the <em>α-glucosidase</em> enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.</p></div>\",\"PeriodicalId\":257,\"journal\":{\"name\":\"Bioorganic Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0045206824006886\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0045206824006886","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Molecular hybridization, synthesis, in vitro α-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds
In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both in vitro and in vivo assays. The tested compounds 7a-7j demonstrated In vitro inhibitory potential against α-glucosidase, as indicated by their IC50 values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC50 value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for in vivo evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both in vitro and in vivo, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the α-glucosidase enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.
期刊介绍:
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.