Pyrogallol is an organic gallic acid converting compound tha
Pyrogallol is an organic gallic acid-converting compound that has three hydroxyl groups and belongs to the phenol family. Gallic PD173955 is obtainable from the galls and barks of various trees, and a simple heating procedure can induce the decarboxylation of gallic acid to produce pyrogallol (alias: pyrogallic acid). A recent study identified pyrogallol in the hot-water extracts of roasted coffee beans as the main inhibitor of xanthine oxidase . Few studies have reported the specific ligand binding mechanisms of pyrogallol to target enzyme molecules [, , ]. However, various functions of pyrogallol have been reported: i) it decreased the growth of Vibrio vulnificus significantly during the log growth phase ; ii) it could be used to coat anucleate, microbial, and mammalian cells without a noticeable decrease in cell viability ; iii) it displayed a synergistic antibiotic effect on Candida tropicalis with fluconazole, along with caffeic acid and gallic acid ; iv) dietary pyrogallol suppressed ductal carcinoma in situ (DCIS) proliferation ; v) it can be a potential natural protective agent against infection through its pro-oxidant activity for different host-pathogen systems ; vi) for agricultural application on litchi fruit during post-harvest storage, pyrogallol displayed beneficial effects on pericarp browning and fruit decay control ; vii) it can be used for measuring the superoxide-scavenging activity of various antioxidants [19,20].
Materials and methods
Discussion Recently and previously, compounds having functional hydroxyl groups have been suggested for various potential utilities and functions: i) chemoselective reactions in the synthesis of complex natural product derivatives and the isolation of natural products ; ii) probing metal ions ; inhibitors of various enzymes [, , ]; anti-inflammatory , antioxidant , and radical scavenging  activities; and myriad other functions and utilities. Typically, pyrogallol derived from natural sources has been studied in the hopes of the discovery and development of pharmacological purposes. Based on our present study, we suggest Annealing pyrogallol is an example of an α-glucosidase inhibitor that may be representative of various phenolic hydroxyl compounds; its analogues or derivatives could be promising in treating type 2 diabetes via inhibition of α-glucosidase, although further study is warranted. The principal findings of our study indicate the following: (1) the kinetic parameters indicate pyrogallol binds to α-glucosidase in a reversible and relatively tight manner; (2) pyrogallol inhibits α-glucosidase activity in a typical mixed-type manner that is related to the induction of a regional conformational change; (3) the inactivation process mediated by pyrogallol occurs quickly, just after the formation of an E-I-S complex, without a conspicuous kinetic process; (4) an overall structural change of α-glucosidase is induced by pyrogallol, which was connected to the loss of enzymatic activity; and, (5) our docking simulation revealed that pyrogallol can interact with several key residues (ASP68, MET69, TYR71, PHE157, PHE158, PHE177, GLN181, HIS348, ASP349, ASP406, VAL407, ASP408, ARG439, and ARG443) in the active site pocket at the early initial binding stage, structurally, hydroxyl groups play key active roles in ligand binding and inhibition, and then, after reaching an equilibrium stage, a stable α-glucosidase-pyrogallol complex was formed via one binding site. Comparison between the kinetic parameters IC50 and K (IC50=0.72±0.051mM; K=0.37±0.018mM) showed that K was smaller than IC50, which indicates that the inhibition was neither a noncompetitive nor uncompetitive type, but tended to be a competitive or mixed-type, based on the classical Cheng and Prusoff equation . Furthermore, subsequent kinetic analysis showed that the pyrogallol-induced inhibition was a pure mixed-type, and fitted well to the classical well-established equations, which properly determined the kinetic dissociation constant.