Combinatorial Synthesis and Virtual Screening of Novel Oxazine and Thiazine Mini Libraries for Antidiabetic Activity

The purpose of the present work was to investigate, following previous works, oxazine and thiazine analogues as antihyperglycemic agent by carrying out docking studies. A series of substituted oxazine and thiazine has been synthesized combinatorially and intermediate compounds were confirmed from the results of chromatographic, spectral and physicochemical analysis. By comparing the interactions of the reference and synthesized molecules with selected target enzymes DPP-4 and glucokinase enzyme, it is clear that the compound can bind strongly with the receptor molecules which suggest that rationale used to optimize structural requirements of ligand with respect to selected targets was appropriate. Two molecules 4-(4-aminophenyl)-6-(2-chloroquinolin-3-yl)-N-pyridin-2-yl-6H-1,3-oxazin-2-amine (A6B3) and 4-(2,4-dimethyl-1H-pyrrol-3-yl)-6-(2,4-dimethoxyphenyl)-N-(pyridin-2-yl)-6H-1,3-oxazin-2-amine-2-carboxylate (A4B3) showed good antidiabetic activity.