Synthesis of New Regioisomers of 5-Nitro-1,4-Naphthoquinone, Evaluation of Antioxidant and Catalase Inhibition Activities

Abstract

The studies on nitronaphthoquinone derivatives are rare in the literature, and the nitro group associated with the aromatic ring in the quinone system is known to increase the biological activity of naphthoquinone due to its electron-withdrawing properties. In the course of quinone derivatives, the new N(H)-substituted-5-nitro-1,4-naphthoquinones (NQ) as regioisomers were synthesized by reactions of 2,3-dichloro-5-nitro-1,4-naphthoquinone with some heterocyclic ring substituted nucleophiles such as anilines, piperazines, or morpholines, according to a Michael 1,4-addition mechanism. Five NQ regioisomer couples having different functional group (2-chloro-isomers 3, 5, 7, 9 and 13; 3-chloro-isomers 2, 4, 6, 8 and 12) are reported here. All new synthesized compounds were characterized by spectroscopic methods and two-dimensional NMR techniques ¹H–¹H correlated spectroscopy (COSY).

The synthesized NQ regioisomers were evaluated for catalase enzyme inhibitory activities and antioxidant efficiency. The synthesized regioisomers were screened for their antioxidant capacity using the cupric-reducing antioxidant capacity (CUPRAC) method. 2-Chloro-3-((2,4-dimethoxyphenyl)amino)-5-nitronaphthalene-1,4-dione (5) showed the highest antioxidant capacity with a 1.80±0.06 CUPRAC-trolox equivalent antioxidant capacity (TEAC) coefficient. Compound 5 also showed strongest catalase enzyme inhibitory activity. The antioxidant capacity results of all 2-chloro regioisomers are higher than the 3-chloro regioisomers. Likewise, also catalase enzyme inhibitory activities results were determined in the same way, except for one regioisomer pair. The catalase was effectively inhibited by the newly synthesized compounds, with % inhibition values in the range of 0.71–0.86%. Some of these NQ compounds also showed remarkable antioxidant capacities.