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

Zhang, Keyu; Wang, Chunmei; Wang, Xiaoyang; Zheng, Haihong; Zhao, Juan; Wang, Mi; Xiao, Sui; Fei, Chenzhong; Zheng, Wenli; Zhang, Lifang; Xue, Feiqun

doi:10.22037/ijpr.2017.2039

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

10.22037/ijpr.2017.2039

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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