Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, cis-Dihydroxylation and Epoxidation

Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic thiophenes. Thiophene oxidative dearomatization pathways involve reactive metabolites, whose detection is important in the pharmaceutical industry, and are catalyzed by monooxygenase (sulfoxidation, epoxidation) and dioxygenase (sulfoxidation, dihydroxylation) enzymes. Sulfoxide and epoxide metabolites of thiophene substrates are often unstable, and, while cis-dihydrodiol metabolites are more stable, significant challenges are presented by both types of metabolite. Prediction of the structure, relative and absolute configuration, and enantiopurity of chiral metabolites obtained from thiophene enzymatic oxidation depends on the substrate, type of oxygenase selected, and molecular docking results. The racemization and dimerization of sulfoxides, cis/trans epimerization of dihydrodiol metabolites, and aromatization of epoxides are all factors associated with the mono- and di-oxygenase-catalyzed metabolism of thiophenes and thiophene-containing drugs and their applications in chemoenzymatic synthesis and medicine.

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Chemoenzymatic synthesis of new derivatives of glycyrrhetinic acid with antiviral activity. Molecular docking study

Bioorganic Chemistry ◽

10.1016/j.bioorg.2018.03.018 ◽

2018 ◽

Vol 78 ◽

pp. 210-219 ◽

Cited By ~ 10

Author(s):

M. Antonela Zígolo ◽

Maximiliano Salinas ◽

Laura Alché ◽

Alicia Baldessari ◽

Guadalupe García Liñares

Keyword(s):

Molecular Docking ◽

Antiviral Activity ◽

Docking Study ◽

Glycyrrhetinic Acid ◽

Chemoenzymatic Synthesis ◽

Molecular Docking Study ◽

Derivatives Of

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Enantioselective, chemoenzymatic synthesis, and absolute configuration of the antioxidant (−)-gloeosporiol

Tetrahedron ◽

10.1016/j.tet.2010.07.074 ◽

2010 ◽

Vol 66 (40) ◽

pp. 8068-8075 ◽

Cited By ~ 7

Author(s):

Gabriela Mancilla ◽

M. Femenía-Ríos ◽

Manuel Grande ◽

R. Hernández-Galán ◽

A.J. Macías-Sánchez ◽

...

Keyword(s):

Absolute Configuration ◽

Chemoenzymatic Synthesis

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Reactive Metabolites: Generation and Estimation with Electrochemistry Based Analytical Strategy as an Emerging Screening Tool

Current Analytical Chemistry ◽

10.2174/1573411016666200131154202 ◽

2020 ◽

Vol 16 (7) ◽

pp. 811-825

Author(s):

Maria Bandookwala ◽

Kavya Sri Nemani ◽

Bappaditya Chatterjee ◽

Pinaki Sengupta

Keyword(s):

Mass Spectrometry ◽

Drug Metabolism ◽

Electrochemical Techniques ◽

In Vivo Studies ◽

Reactive Metabolites ◽

Electrochemical Cells ◽

Simulation Studies ◽

Analytical Strategy ◽

Analytical Approaches

Background: Analytical scientists have constantly been in search for more efficient and economical methods for drug simulation studies. Owing to great progress in this field, there are various techniques available nowadays that mimic drug metabolism in the hepatic microenvironment. The conventional in vitro and in vivo studies pose inherent methodological drawbacks due to which alternative analytical approaches are devised for different drug metabolism experiments. Methods: Electrochemistry has gained attention due to its benefits over conventional metabolism studies. Because of the protein binding nature of reactive metabolites, it is difficult to identify them directly after formation, although the use of trapping agents aids in their successful identification. Furthermore, various scientific reports confirmed the successful simulation of drug metabolism studies by electrochemical cells. Electrochemical cells coupled with chromatography and mass spectrometry made it easy for direct detection of reactive metabolites. In this review, an insight into the application of electrochemical techniques for metabolism simulation studies has been provided. The sole use of electrochemical cells, as well as their setups on coupling to liquid chromatography and mass spectrometry has been discussed. The importance of metabolism prediction in early drug discovery and development stages along with a brief overview of other conventional methods has also been highlighted. Conclusion: To the best of our knowledge, this is the first article to review the electrochemistry based strategy for the analysis of reactive metabolites. The outcome of this ‘first of its kind’ review will significantly help the researchers in the application of electrochemistry based bioanalysis for metabolite detection.

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