Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents.

In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a-o was carried out using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a-o exhibited good α-glucosidase inhibition with IC50 values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC50 = 752.0 ± 2.0 µM). Structure-activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations.

Ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate in the smiles rearrangement reaction: straightforward synthesis of amino acid derived quinolin-2(1H)-one enamines.

This paper describes the development of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate compound as a heterocyclic enols containing a Michael acceptor so that it participates in an Ugi-type multicomponent condensation through a Smiles rearrangement in replacement of acid components. The new four-component containing 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate, aldehyde derivatives, amine derivatives and isocyanides process leads readily and efficiently to heterocyclic enamines. This report is an outstanding strategy for the preparation of new biologically structures containing peptidic or pseudo-peptidic with quinolin-2(1H)-one scaffolds.