One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors

Abstract

A green and efficient one-pot multi-component protocol was developed for the synthesis of some novel dihydrochromeno[4,3-b]pyrrol-3-yl derivatives through the reaction of arylglyoxals, malono derivatives, and different 4-amino coumarins in ethanol at reflux condition. In this method, all products were obtained in good to excellent yield. Next, all synthesized derivatives were evaluated for their α-glucosidase inhibitory activity. Most of the compounds displayed potent inhibitory activities with IC 50 values in the range of 48.65 ± 0.01–733.83 ± 0.10 μM compared to the standard inhibitor acarbose (IC 50 = 750.90 ± 0.14 μM). The kinetic study of compound 5e as the most potent derivative (IC 50 = 48.65 ± 0.01 μM) showed a competitive mechanism with a K i value of 42.6 µM. Moreover, docking studies revealed that dihydrochromeno[4,3-b]pyrrol-3-yl effectively interacted with important residues in the active site of α-glucosidase. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10337-w.

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

“…α-Glucosidase has 18 tryptophan residues that eight are exposed to the solvent, and four are found in the proposed active site pocket (Trp381, Trp710, Trp715, and Trp789). Therefore, the conformation of the enzyme affected by the local tryptophan environment, can be followed by the change of fluorescence intensity 43 , 44 . In fact, fluorescence spectroscopy measurements could be used to predict the tertiary structure of the enzyme.…”

“…The molecular docking of compounds 9b and 9e was performed using the maestro molecular modeling platform (version 10.5), Schrödinger suites 50 . X-ray crystallographic structure of α-glucosidase in complex with acarbose (PDB ID: 5NN8) was obtained from www.rcsb.com 44 . A protein preparation wizard was used to remove water molecules and co-crystallized atoms from the protein and prepare the receptor.…”

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors

“…A Lineweaver–Burk plot was generated to identify the type of inhibition and the Michaelis–Menten constant ( K m ) value was determined from the plot between reciprocal of the substrate concentration (1/[S]) and reciprocal of enzyme rate (1/V) over various inhibitor concentrations. The experimental inhibitor constant ( K i ) value was constructed by secondary plots of the inhibitor concentration [I] versus K m [ 43 , 54 ].…”

“…The molecular docking investigation of all derivatives were performed using the maestro molecular modeling platform (version 10.5), Schrödinger suites [ 55 ]. X-ray crystallographic structure of α-glucosidase 5NN8 was downloaded from the PDB website ( https://www.rcsb.org/ ) [ 54 ]. A protein preparation wizard was used to remove water molecules and co-crystallized atoms from the protein and prepare the receptor.…”

Design, synthesis, and in silico studies of quinoline-based-benzo[d]imidazole bearing different acetamide derivatives as potent α-glucosidase inhibitors

“…In the last few decades, different synthetic small molecules including benzo[d]imidazole 20 , isatin 21 benzo[b]thiophene 22 pyrimidine 23 , xanthone 24 , chromene 6 , azole 18 , 25 against α-glucosidase attracted increasing attention.…”