Design, synthesis and α-glucosidase inhibition study of novel pyridazin-based derivatives

In this paper, pyridazin derivatives containing different thiobenzyl moieties were synthesized and screened for their inhibitory activities against rat intestinal α-glucosidase enzyme. The final products were easily obtained without the need to harsh purification steps. The in vitro results revealed...

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Bibliographic Details
Published in:Medicinal chemistry research 2023-04, Vol.32 (4), p.713-722
Main Authors: Firoozpour, Loghman, Kazemzadeh Arasi, Faraz, Toolabi, Mahsa, Moghimi, Setareh, Armandeh, Maryam, Salmani, Farzaneh, Pakrad, Roya, Firuzpour, Hadis, Ghasemi Dogaheh, Mahtab, Ebrahimi, Seyed Esmaeil Sadat, H.M.E. Ketabforoosh, Shima, Karima, Saeed, Foroumadi, Alireza
Format: Article
Language:English
Subjects:
Acarbose
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Glucosidase
Hydrogen bonding
Inorganic Chemistry
Medicinal Chemistry
Original Research
Pharmacology/Toxicology
Synthesis
α-Glucosidase
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Summary:In this paper, pyridazin derivatives containing different thiobenzyl moieties were synthesized and screened for their inhibitory activities against rat intestinal α-glucosidase enzyme. The final products were easily obtained without the need to harsh purification steps. The in vitro results revealed that all the synthesized compounds were more potent (IC 50 s = 26.3–148.9 μM) than the clinically used drug, acarbose. The kinetic study revealed the competitive inhibition behavior of compound 5m (K i  = −56 μM). Docking studies showed imperative interactions such as hydrogen bonding, Pi-Pi T-shaped, and Pi-anion interactions confirming the observed activity. The RMSD value was determined less than 3 Å and validated the study. Graphical Abstract
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-023-03027-9