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.

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Journal Article | Research Support, Non-U.S. Gov't

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Peytam F, Hosseini FS, Hekmati M, Bayati B, Moghadam MS, Emamgholipour Z, Firoozpour L, Mojtabavi S, Faramarzi MA, Sadat-Ebrahimi SE, ... Show all

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