{"title":"具有二氢吡喃[3,2-c]喹啉骨架的优秀合成α-葡萄糖苷酶抑制剂的体内抗糖尿病和降脂评价。","authors":"Maryam Mohammadi-Khanaposhtani, Navid Bakhtiari, Fatemeh Bandarian, Bagher Larijani, Mohammad Mahdavi, Hossein Najafzadehvarzi","doi":"10.1007/s40200-024-01505-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The <i>in vivo</i> assay is a key step in the development of a new bioactive compound as a lead drug structure. Based on importance of α-glucosidase inhibitors in the control of blood glucose level (BGL) in diabetes, in the present work, 3-amino-1-(4-chlorophenyl)-12-oxo-11,12-dihydro-1<i>H</i>-benzo[<i>h</i>]pyrano[3,2-<i>c</i>]quinoline-2-carbonitrile (<b>ACODDHBPQC</b>) that showed excellent inhibitory activity on the yeast form of α-glucosidase was selected for <i>in vivo</i> anti-diabetic assay.</p><p><strong>Methods: </strong>The <i>in vivo</i> anti-diabetic and anti-lipidemic effects of this synthetic compound were evaluated using by a streptozotocin (STZ)-induced diabetic Wistar rat model. <i>In silico</i> docking study of <b>ACODDHBPQC</b> was performed by Atodock tools and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of this compound was predicted by PreADMT online software.</p><p><strong>Results: </strong>The obtained results revealed that selected compound <b>ACODDHBPQC</b> showed a significant anti-diabetic effect on diabetic rats. In vivo anti-lipidemic assay also demonstrated that <b>ACODDHBPQC</b> had favorable effects on cholesterol and LDL levels. Furthermore, <i>in silico</i> studies showed that <b>ACODDHBPQC</b> interacted with key residues of the α-glucosidase active site and had good pharmacokinetic and toxicity properties.</p><p><strong>Conclusion: </strong>In summary, anti-hyperglycemic effects of <b>ACODDHBPQC</b> was confirmed by <i>in vivo</i> study. However, more evaluations are needed to introduce <b>ACODDHBPQC</b> as a lead drug compound.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":15635,"journal":{"name":"Journal of Diabetes and Metabolic Disorders","volume":"23 2","pages":"2375-2384"},"PeriodicalIF":1.8000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599671/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>In vivo</i> anti-diabetic and anti-lipidemic evaluations of an excellent synthetic α-glucosidase inhibitor with dihydropyrano[3,2-c]quinoline skeleton.\",\"authors\":\"Maryam Mohammadi-Khanaposhtani, Navid Bakhtiari, Fatemeh Bandarian, Bagher Larijani, Mohammad Mahdavi, Hossein Najafzadehvarzi\",\"doi\":\"10.1007/s40200-024-01505-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The <i>in vivo</i> assay is a key step in the development of a new bioactive compound as a lead drug structure. Based on importance of α-glucosidase inhibitors in the control of blood glucose level (BGL) in diabetes, in the present work, 3-amino-1-(4-chlorophenyl)-12-oxo-11,12-dihydro-1<i>H</i>-benzo[<i>h</i>]pyrano[3,2-<i>c</i>]quinoline-2-carbonitrile (<b>ACODDHBPQC</b>) that showed excellent inhibitory activity on the yeast form of α-glucosidase was selected for <i>in vivo</i> anti-diabetic assay.</p><p><strong>Methods: </strong>The <i>in vivo</i> anti-diabetic and anti-lipidemic effects of this synthetic compound were evaluated using by a streptozotocin (STZ)-induced diabetic Wistar rat model. <i>In silico</i> docking study of <b>ACODDHBPQC</b> was performed by Atodock tools and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of this compound was predicted by PreADMT online software.</p><p><strong>Results: </strong>The obtained results revealed that selected compound <b>ACODDHBPQC</b> showed a significant anti-diabetic effect on diabetic rats. In vivo anti-lipidemic assay also demonstrated that <b>ACODDHBPQC</b> had favorable effects on cholesterol and LDL levels. Furthermore, <i>in silico</i> studies showed that <b>ACODDHBPQC</b> interacted with key residues of the α-glucosidase active site and had good pharmacokinetic and toxicity properties.</p><p><strong>Conclusion: </strong>In summary, anti-hyperglycemic effects of <b>ACODDHBPQC</b> was confirmed by <i>in vivo</i> study. However, more evaluations are needed to introduce <b>ACODDHBPQC</b> as a lead drug compound.</p><p><strong>Graphical abstract: </strong></p>\",\"PeriodicalId\":15635,\"journal\":{\"name\":\"Journal of Diabetes and Metabolic Disorders\",\"volume\":\"23 2\",\"pages\":\"2375-2384\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-10-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599671/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Diabetes and Metabolic Disorders\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s40200-024-01505-4\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Diabetes and Metabolic Disorders","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40200-024-01505-4","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
In vivo anti-diabetic and anti-lipidemic evaluations of an excellent synthetic α-glucosidase inhibitor with dihydropyrano[3,2-c]quinoline skeleton.
Objectives: The in vivo assay is a key step in the development of a new bioactive compound as a lead drug structure. Based on importance of α-glucosidase inhibitors in the control of blood glucose level (BGL) in diabetes, in the present work, 3-amino-1-(4-chlorophenyl)-12-oxo-11,12-dihydro-1H-benzo[h]pyrano[3,2-c]quinoline-2-carbonitrile (ACODDHBPQC) that showed excellent inhibitory activity on the yeast form of α-glucosidase was selected for in vivo anti-diabetic assay.
Methods: The in vivo anti-diabetic and anti-lipidemic effects of this synthetic compound were evaluated using by a streptozotocin (STZ)-induced diabetic Wistar rat model. In silico docking study of ACODDHBPQC was performed by Atodock tools and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of this compound was predicted by PreADMT online software.
Results: The obtained results revealed that selected compound ACODDHBPQC showed a significant anti-diabetic effect on diabetic rats. In vivo anti-lipidemic assay also demonstrated that ACODDHBPQC had favorable effects on cholesterol and LDL levels. Furthermore, in silico studies showed that ACODDHBPQC interacted with key residues of the α-glucosidase active site and had good pharmacokinetic and toxicity properties.
Conclusion: In summary, anti-hyperglycemic effects of ACODDHBPQC was confirmed by in vivo study. However, more evaluations are needed to introduce ACODDHBPQC as a lead drug compound.
期刊介绍：
Journal of Diabetes & Metabolic Disorders is a peer reviewed journal which publishes original clinical and translational articles and reviews in the field of endocrinology and provides a forum of debate of the highest quality on these issues. Topics of interest include, but are not limited to, diabetes, lipid disorders, metabolic disorders, osteoporosis, interdisciplinary practices in endocrinology, cardiovascular and metabolic risk, aging research, obesity, traditional medicine, pychosomatic research, behavioral medicine, ethics and evidence-based practices.As of Jan 2018 the journal is published by Springer as a hybrid journal with no article processing charges. All articles published before 2018 are available free of charge on springerlink.Unofficial 2017 2-year Impact Factor: 1.816.
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