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, H-1-, and (CNMR)-C-13 spectroscopic techniques. All compounds were subjected to their in vitro alpha-glucosidase inhibitory activity. Results showed that except compound 1-3, 5, 7, and 22, all compounds were found potent and showed many folds increased alpha-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 +/- 10.0 mu M). Compound 13 (IC50 = 85.0 +/- 0.5 mu M) 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.
[GRAPHICS]
.