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Synthesis and In Silico Analysis of New Polyheterocyclic Molecules Derived from [1,4]-Benzoxazin-3-one and Their Inhibitory Effect against Pancreatic α-Amylase and Intestinal α-Glucosidase.

Authors :
Ellouz, Mohamed
Ihammi, Aziz
Baraich, Abdellah
Farihi, Ayoub
Addichi, Darifa
Loughmari, Saliha
Sebbar, Nada Kheira
Bouhrim, Mohamed
Mothana, Ramzi A.
Noman, Omar M.
Eto, Bruno
Chigr, Fatiha
Chigr, Mohammed
Source :
Molecules. Jul2024, Vol. 29 Issue 13, p1-17. 17p. 1 Diagram, 4 Charts, 4 Graphs.
Publication Year :
2024

Abstract

This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin3-one derivatives 5a–5o. The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a “click chemistry” approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including 1H NMR, 13C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of −9.9 and −9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski’s criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14203049
Volume :
29
Issue :
13
Database :
Academic Search Index
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
179356989
Full Text :
https://doi.org/10.3390/molecules29133086