| Autor: |
Ellouz M; Laboratory of Molecular Chemistry, Materials and Catalysis (LCMMC), Faculty of Sciences and Technology, Sultan Moulay Slimane University, P.O. Box 523, Beni-Mellal 23000, Morocco., Ihammi A; Laboratory of Molecular Chemistry, Materials and Catalysis (LCMMC), Faculty of Sciences and Technology, Sultan Moulay Slimane University, P.O. Box 523, Beni-Mellal 23000, Morocco., Baraich A; Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Boulevard Mohamed VI, P.O. Box 717, Oujda 60000, Morocco., Farihi A; Laboratory of Biology and Health, Faculty of Sciences, Ibn Tofail University, Kenitra 14000, Morocco.; Oriental Center for Water and Environmental Sciences and Technologies (COSTE), Mohammed Premier University, Oujda 60000, Morocco., Addichi D; Laboratory of Molecular Chemistry, Materials and Catalysis (LCMMC), Faculty of Sciences and Technology, Sultan Moulay Slimane University, P.O. Box 523, Beni-Mellal 23000, Morocco., Loughmari S; Laboratory of Molecular Chemistry, Materials and Catalysis (LCMMC), Faculty of Sciences and Technology, Sultan Moulay Slimane University, P.O. Box 523, Beni-Mellal 23000, Morocco., Sebbar NK; Laboratory of Organic and Physical Chemistry, Applied Bioorganic Chemistry Team, Faculty of Sciences, Ibnou Zohr University, Agadir 80000, Morocco., Bouhrim M; Biological Engineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal 23000, Morocco.; Laboratoires TBC, Laboratory of Pharmacology, Pharmacokinetics, and Clinical Pharmacy, Faculty of Pharmaceutical and Biological Sciences, P.O. Box 83, F-59000 Lille, France., A Mothana R; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia., M Noman O; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia., Eto B; Laboratoires TBC, Laboratory of Pharmacology, Pharmacokinetics, and Clinical Pharmacy, Faculty of Pharmaceutical and Biological Sciences, P.O. Box 83, F-59000 Lille, France., Chigr F; Biological Engineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal 23000, Morocco., Chigr M; Laboratory of Molecular Chemistry, Materials and Catalysis (LCMMC), Faculty of Sciences and Technology, Sultan Moulay Slimane University, P.O. Box 523, Beni-Mellal 23000, Morocco. |
| Abstrakt: |
This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-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 1 H NMR, 13 C 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. |
