Abstract

Abstract

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications.

Details

Title
Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights
Author
Abdelrahman Hamdi 1 ; Yaseen, Muhammad 2 ; Ewes, Wafaa A 1 ; Mashooq Ahmad Bhat 3 ; Ziedan, Noha I 4 ; El-Shafey, Hamed W 1 ; Mohamed, Ahmed A B 5 ; Elnagar, Mohamed R 6 ; Haikal, Abdullah 7 ; Othman, Dina I A 1 ; Elgazar, Abdullah A 8 ; Abusabaa, Ahmed H A 9 ; Abdelrahman, Kamal S 10 ; Soltan, Osama M 10 ; Elbadawi, Mostafa M 11 

1  Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt 
2  Institute of Chemical Sciences, University of Swat , Swat , Pakistan 
3  Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University , Riyadh , Saudi Arabia 
4  Department of physical, mathematical and Engineering science, Faculty of science, Business and Enterprise, University of Chester , Chester , UK 
5  Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt 
6  Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University , Cairo , Egypt, Department of Pharmacology, College of Pharmacy, The Islamic University , Najaf , Iraq 
7  Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt 
8  Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University , Kafrelsheikh , Egypt 
9  Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, Fayoum University , Fayoum , Egypt 
10  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University , Assiut , Egypt 
11  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University , Kafrelsheikh , Egypt 
Publication year
2023
Publication date
Dec 2023
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/14756366.2023.2231170
ProQuest document ID
2917549179
Copyright
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.. This work is licensed under the Creative Commons  Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.