AUTHOR=Boyd Derek R. , Sharma Narain D. , Loke Pui L. , Carroll Jonathan G. , Stevenson Paul J. , Hoering Patrick , Allen Christopher C. R. 

TITLE=Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2020.619175

DOI=10.3389/fbioe.2020.619175

ISSN=2296-4185

ABSTRACT=<p>Molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase (TDO), were conducted using Autodock Vina, to identify novel edge-to-face interactions and to rationalize the observed stereoselective <italic>cis</italic>-dihydroxylation of carbocyclic rings and formation of isolable <italic>cis</italic>-dihydrodiol metabolites. These <italic>in silico</italic> docking results of quinoline and pyridine substrates, with TDO, also provided support for the postulated <italic>cis</italic>-dihydroxylation of electron-deficient pyridyl rings, to give transient <italic>cis</italic>-dihydrodiol intermediates and the derived hydroxyquinolines. 2-Chloroquinoline <italic>cis</italic>-dihydrodiol metabolites were used as precursors in the chemoenzymatic synthesis of enantiopure arene oxide and arene dioxide derivatives of quinoline, in the context of its possible mammalian metabolism and carcinogenicity.</p>