Modification of 6,7-Dichloro-5,8-Quinolinedione at C2 Position: Synthesis, Quantum Chemical Properties, and Activity against DT-Diaphorase Enzyme

Author:

Kadela-Tomanek Monika1ORCID,Bębenek Ewa1ORCID,Chrobak Elwira1ORCID

Affiliation:

1. Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland

Abstract

This research presents a synthesis and characterization of new 6,7-dichloro-5,8-quinolinedione derivatives with various groups at the C2 position. Chemical structures were examined by the spectroscopic methods. The quantum chemical parameters calculated using the DFT method showed that these derivatives are highly reactive towards the nucleophilic target. The molecular electrostatic potential map (MEP) showed that nucleophilic regions are localized near the nitrogen atom and the formyl group. Introduction of the hydroxyl or formyl groups at the C2 position led to the formation of an additional nucleophilic region. New compounds were tested as substrates for the NQO1 protein. An enzymatic study showed that derivatives are a good substrate for the NQO1 enzyme. Moreover, it was shown that the enzymatic conversion rates depend on the type of substituent at the C2 position of the 5,8-quinolinedione scaffold. A molecular docking study was used to study the interaction between new derivatives and the NQO1 protein. The arrangement and type of interactions between derivatives and the NQO1 enzyme depended on the type of substituent at the C2 position. A derivative with the hydroxyl group at this position was found to form an additional hydrogen bond between the formyl group and the tyrosine.

Publisher

MDPI AG

Subject

Fluid Flow and Transfer Processes,Computer Science Applications,Process Chemistry and Technology,General Engineering,Instrumentation,General Materials Science

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