Dihydroquinazolin-4(1H)-one derivatives as novel and potential leads for diabetic management

A variety of dihydroquinazolin-4(1 H )-one derivatives ( 1–37 ) were synthesized via “one-pot” three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectr...

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Published in:Molecular diversity 2022-04, Vol.26 (2), p.849-868
Main Authors: Babatunde, Oluwatoyin, Hameed, Shehryar, Salar, Uzma, Chigurupati, Sridevi, Wadood, Abdul, Rehman, Ashfaq Ur, Venugopal, Vijayan, Khan, Khalid Mohammed, Taha, Muhammad, Perveen, Shahnaz
Format: Article
Language:English
Subjects:
alpha-Amylases - metabolism
alpha-Glucosidases - chemistry
Biochemistry
Biomedical and Life Sciences
Diabetes Mellitus
Enzymes
Glycoside Hydrolase Inhibitors - chemistry
Glycoside Hydrolase Inhibitors - pharmacology
Humans
Hyperglycemia
Kinetics
Life Sciences
Magnetic Resonance Spectroscopy
Molecular Docking Simulation
Organic Chemistry
Original Article
Pharmacy
Polymer Sciences
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Summary:A variety of dihydroquinazolin-4(1 H )-one derivatives ( 1–37 ) were synthesized via “one-pot” three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1 H-, and 13 C-NMR. Compounds were subjected to α -amylase and α -glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α -amylase (IC 50  = 23.33 ± 0.02—88.65 ± 0.23 μM) and α -glucosidase (IC 50  = 25.01 ± 0.12—89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC 50  = 17.08 ± 0.07 μM for α -amylase and IC 50  = 17.67 ± 0.09 μM for α -glucosidase). Structure–activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α -amylase and non-competitive inhibition for α -glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.
ISSN:1381-1991
1573-501X
DOI:10.1007/s11030-021-10196-5