In vivo anti-diabetic and anti-lipidemic evaluations of an excellent synthetic α-glucosidase inhibitor with dihydropyrano[3,2-c]quinoline skeleton.

IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Journal of Diabetes and Metabolic Disorders Pub Date : 2024-10-05 eCollection Date: 2024-12-01 DOI:10.1007/s40200-024-01505-4

Maryam Mohammadi-Khanaposhtani, Navid Bakhtiari, Fatemeh Bandarian, Bagher Larijani, Mohammad Mahdavi, Hossein Najafzadehvarzi

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Abstract

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.

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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。

目的：体内试验是开发新的生物活性化合物作为先导药物结构的关键步骤。基于α-葡萄糖苷酶抑制剂在糖尿病患者血糖水平控制中的重要性，本文选择了对α-葡萄糖苷酶酵母菌具有良好抑制活性的3-氨基-1-（4-氯苯基）-12-氧-11,12-二氢- 1h -苯并[h]吡喃[3,2-c]喹啉-2-碳腈（ACODDHBPQC）进行体内抗糖尿病实验。方法：采用链脲佐菌素（STZ）诱导的糖尿病大鼠模型，观察该化合物的体内抗糖尿病和降脂作用。利用Atodock工具进行ACODDHBPQC的硅对接研究，并利用PreADMT在线软件预测该化合物的吸收、分布、代谢、排泄和毒性（ADMET）特性。结果：所选化合物ACODDHBPQC对糖尿病大鼠具有明显的抗糖尿病作用。体内抗血脂实验也表明，ACODDHBPQC对胆固醇和LDL水平有良好的影响。此外，硅片研究表明，ACODDHBPQC与α-葡萄糖苷酶活性位点的关键残基相互作用，具有良好的药代动力学和毒性。结论：综上所述，体内实验证实了ACODDHBPQC的抗高血糖作用。然而，ACODDHBPQC作为先导药物的引入还需要更多的评价。图形化的简介:

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来源期刊

Journal of Diabetes and Metabolic Disorders Medicine-Internal Medicine

CiteScore

4.80

自引率

3.60%

发文量

210

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.