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

• Published in: Frontiers in bioengineering and biotechnology Vol. 8; p. 619175
• Main Authors: Boyd, Derek R, Sharma, Narain D, Loke, Pui L, Carroll, Jonathan G, Stevenson, Paul J, Hoering, Patrick, Allen, Christopher C R
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12-02-2021
• Subjects: arene oxides; biocatalysis; Bioengineering and Biotechnology; cis-dihydrodiols; dioxygenase; docking; dioxygenase; docking; arene oxides; biocatalysis; cis-dihydrodiols
• ISSN: 2296-4185; 2296-4185
• DOI: 10.3389/fbioe.2020.619175

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
-dihydroxylation of carbocyclic rings and formation of isolable
-dihydrodiol metabolites. These
docking results of quinoline and pyridine substrates, with TDO, also provided support for the postulated
-dihydroxylation of electron-deficient pyridyl rings, to give transient
-dihydrodiol intermediates and the derived hydroxyquinolines. 2-Chloroquinoline
-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.