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

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.