Nirvana A Gohar, Eman A Fayed, Yousry A Ammar, Ola A Abu Ali, Ahmed Ragab, Amal M Mahfoz, Moustafa S Abusaif
{"title":"Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting <i>α</i>-amylase, and <i>α</i>-glucosidase: synthesis, molecular docking, and ADMET studies.","authors":"Nirvana A Gohar, Eman A Fayed, Yousry A Ammar, Ola A Abu Ali, Ahmed Ragab, Amal M Mahfoz, Moustafa S Abusaif","doi":"10.1080/14756366.2024.2367128","DOIUrl":null,"url":null,"abstract":"<p><p>Inhibition of α-glucosidase and <i>α</i>-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-<i>b</i>] quinoxalines-carrying thiazole hybrids <b>1-17</b> were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds <b>4</b>, <b>6</b>, <b>8</b>, and <b>16</b> were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against <i>α</i>-glucosidase and <i>α</i>-amylase enzymes <i>in vitro</i>. The four hybrids <b>4</b>, <b>6</b>, <b>8</b>, and <b>16</b> represented moderate to potent activity with IC<sub>50</sub> values 0.982 ± 0.04, to 10.19 ± 0.21 for <i>α</i>-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for <i>α</i>-amylase inhibition when compared to the standard medication acarbose with IC<sub>50</sub>=0.316 ± 0.02 μM for <i>α</i>-glucosidase inhibition and 31.56 ± 1.33 μM for <i>α</i>-amylase inhibition. Docking studies as well as <i>in silico</i> ADMT were done.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2367128"},"PeriodicalIF":5.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC467095/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Enzyme Inhibition and Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14756366.2024.2367128","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1-17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 μM for α-glucosidase inhibition and 31.56 ± 1.33 μM for α-amylase inhibition. Docking studies as well as in silico ADMT were done.
期刊介绍:
Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents.
Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research.
The journal’s focus includes current developments in:
Enzymology;
Cell biology;
Chemical biology;
Microbiology;
Physiology;
Pharmacology leading to drug design;
Molecular recognition processes;
Distribution and metabolism of biologically active compounds.