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In Vivo Anti-Diabetic and Anti-Lipidemic Evaluations of an Excellent Synthetic Α-Glucosidase Inhibitor With Dihydropyrano[3,2-C]Quinoline Skeleton Publisher



Mohammadikhanaposhtani M1 ; Bakhtiari N2 ; Bandarian F3 ; Larijani B4 ; Mahdavi M4 ; Najafzadehvarzi H1
Authors
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Authors Affiliations
  1. 1. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  2. 2. Faculty of Pharmacy, Islamic Azad University, Ayatollah Amoli Branch, Amol, Iran
  3. 3. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Diabetes and Metabolic Disorders Published:2024


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. Graphical abstract: (Figure presented.) © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024.
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