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Imidazo[1,2-C]Quinazolines As a Novel and Potent Scaffold of Α-Glucosidase Inhibitors: Design, Synthesis, Biological Evaluations, and in Silico Studies Publisher Pubmed



Peytam F1 ; Hosseini F2 ; Hekmati M2 ; Bayati B3 ; Moghadam MS3 ; Emamgholipour Z3 ; Firoozpour L3 ; Mojtabavi S4 ; Faramarzi MA4 ; Sadatebrahimi SE3 ; Tehrani MB3 ; Foroumadi A1, 3
Authors
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Authors Affiliations
  1. 1. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Organic Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  3. 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Scientific Reports Published:2023


Abstract

α-Glucosidase inhibition is an approved treatment for type 2 diabetes mellitus (T2DM). In an attempt to develop novel anti-α-glucosidase agents, two series of substituted imidazo[1,2-c]quinazolines, namely 6a–c and 11a–o, were synthesized using a simple, straightforward synthetic routes. These compounds were thoroughly characterized by IR, 1H and 13C NMR spectroscopy, as well as mass spectrometry and elemental analysis. Subsequently, the inhibitory activities of these compounds were evaluated against Saccharomyces cerevisiae α-glucosidase. In present study, acarbose was utilized as a positive control. These imidazoquinazolines exhibited excellent to great inhibitory potencies with IC50 values ranging from 12.44 ± 0.38 μM to 308.33 ± 0.06 μM, which were several times more potent than standard drug with IC50 value of 750.0 ± 1.5 μM. Representatively, compound 11j showed remarkable anti-α-glucosidase potency with IC50 = 12.44 ± 0.38 μM, which was 60.3 times more potent than positive control acarbose. To explore the potential inhibition mechanism, further evaluations including kinetic analysis, circular dichroism, fluorescence spectroscopy, and thermodynamic profile were carried out for the most potent compound 11j. Moreover, molecular docking studies and in silico ADME prediction for all imidazoquinazolines 6a–c and 11a–o were performed to reveal their important binding interactions, as well as their physicochemical and drug-likeness properties, respectively. © 2023, Springer Nature Limited.
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