Synthesis, In Vitro activity and Metabolic Properties of Quinocetone and Structurally Similar Compounds

Document Type: Research article

Authors

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences

Abstract

To investigate the cytotoxicity mechanism of quinocetone from the perspective of chemical structure, quinocetone and other new quinoxaline-1,4-dioxide derivatives were synthesized, and evaluated for their activities, and analysed for the metabolic characteristics. Quinocetone and other new quinoxaline-1,4-dioxide derivatives were synthesized, and evaluated for their activities, and analysed for the metabolic characteristics. The synthetic route started from 2-nitroaniline which was reacted with 3-bromopropanoic acid followed by the reaction of acetylacetone to afford 2-acetyl-3-methylquinoxaline-1,4-dioxide. The aldol condensation of the later compound with aromatic aldehydes led to the formation of the quinocetone structure similar compounds. A number of prepared derivatives exerted antimicrobial activities and cytotoxicity potency. Analysis of metabolic pathways in vitro displayed 2-propenyl and N→O groups were the major sites. The results suggested 2-propenyl group exert important role in cytotoxicity of quinocetone and is another major toxiccophore for quinocetone, and different electronic substituents in arylidene aryl ring could affect the electronic arrangement of 2-propenyl and N→O groups to chang the cytostatic potency.

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