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

Frontiers in Bioengineering and Biotechnology

Patrick Hoering¹  Christopher C. R. Allen¹  Jonathan G. Carroll²  Pui L. Loke²  Paul J. Stevenson²  Narain D. Sharma²  Derek R. Boyd² 

[1] School of Biological Sciences, Queen's University of Belfast, Belfast, United Kingdom;School of Chemistry and Chemical Engineering, Queen's University of Belfast, Belfast, United Kingdom;

关键词: arene oxides;    cis-dihydrodiols;    dioxygenase;    docking;    biocatalysis;   

DOI  :  10.3389/fbioe.2020.619175

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown