Tehran University of Medical Sciences

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Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors Publisher



Wali H1 ; Anwar A2 ; Shamim S1 ; Khan KM1, 3 ; Mahdavi M4 ; Salar U5 ; Larijani B4 ; Perveen S6 ; Taha M3 ; Faramarzi MA7
Authors

Source: Journal of the Iranian Chemical Society Published:2021


Abstract

Functionalized quinazolinone derivatives 1–30 were synthesized by two-step reaction. First, anthranilic acid was treated with substituted phenyl isothiocyanate to synthesize 3-aryl-2-thioxo-2,3-dihydroquinazolinone derivatives 1–8 which in turn reacted with different bromoacetophenone derivatives to obtain fully functionalized quinazolinone derivatives 9–30. Both reactions were catalyzed by triethylamine. All the products were characterized by EI-, HREI-MS, 1H-, and 13CNMR spectroscopic techniques. All compounds were subjected to their in vitro α-glucosidase inhibitory activity. Results showed that except compound 1–3, 5, 7, and 22, all compounds were found potent and showed many folds increased α-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 ± 10.0 µM). Compound 13 (IC50 = 85.0 ± 0.5 µM) was recognized as the most potent analog of the whole series, with ninefold enhanced inhibitory potential than the standard acarbose. Compounds 1–9, 11, 12, 22, and 26 were structurally known compounds, while remaining all are new. Kinetic study on compound 13 showed that the compound is following a competitive-type inhibition mechanism. Furthermore, in silico studies have also been performed to better rationalize the interactions between synthetic compound and active site of the enzyme. Graphic abstract: [Figure not available: see fulltext.] © 2021, Iranian Chemical Society.
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