BioChem - DOS

3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors

Molecules : a journal of synthetic chemistry and natural product chemistry

Lozinskaya, Natalia A.; Bezsonova, Elena N.; Dubar, Meriam; Melekhina, Daria D.; Bazanov, Daniil R.; Bunev, Alexander S.; Grigor’eva, Olga B.; Klochkov, Vladlen G.; Sokolova, Elena V.; Babkov, Denis A.; Spasov, Alexander A.; Sosonyuk, Sergey E.

<P>The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2. Herein, we report the synthesis and study of 3-arylidene-2-oxindoles as novel NRH:quinone oxidoreductase inhibitors. It was demonstrated that oxindoles with 6-membered aryls in the arylidene moiety were obtained predominantly as <I>E</I>-isomers while for some 5-membered aryls, the <I>Z</I>-isomers prevailed. The most active compounds inhibited NQO2 with an IC<SUB>50</SUB> of 0.368 &micro;M. The presence of a double bond in the oxindoles was crucial for NQO2 inhibition activity. There was no correlation between NQO2 inhibition activity of the synthesized compounds and their cytotoxic effect on the A549 cell line.</P>

2023

MDPI

1420-3049

28

3

pp.1174

10.3390/molecules28031174

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART122807432

oxindoles; indolin-2-ones; NQO2; NRH:quinone oxidoreductase 2; 3-arylidene-2-oxindoles; anticancer