Synthesis of 3-[(N-Carboalkoxy)ethylamino]-Indazole-Dione Derivatives and Their Biological Activities on Human Liver Carbonyl Reductase

Solomon Berhe, Andrew Slupe, Choice Luster, Henry A. Charlier, Don L. Warner, Leon H. Zalkow, Edward M. Burgess, Nkechi M. Enwerem, Oladapo Bakare

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

A series of indazole-dione derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of appropriate substituted benzoquinones or naphthoquinones and N -carboalkoxyamino diazopropane derivatives. These compounds were evaluated for their effects on human carbonyl reductase. Several of the analogs were found to serve as substrates for carbonyl reductase with a wide range of catalytic efficiencies, while four analogs display inhibitory activities with IC 50 values ranging from 3–5 μM. Two of the inhibitors were studied in greater detail and were found to be noncompetitive inhibitors against both NADPH and menadione with K I values ranging between 2 and 11 μM. Computational studies suggest that conformation of the compounds may determine whether the indazole-diones bind productively to yield product or nonproductively to inhibit the enzyme.

Original languageAmerican English
JournalChemistry and Biochemistry Faculty Publications and Presentations
DOIs
StatePublished - 1 Jan 2010

EGS Disciplines

  • Chemistry

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