Author/Authors :
Zhang, Keyu Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Wang, Chunmei Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Wang, Xiaoyang Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Zheng, Haihong Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Zhao, Juan Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Wang, Mi Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Xiao, Sui Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Fei, Chenzhong Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Zheng, Wenli Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Zhang, Lifang Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China , Xue, Feiqun Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research - Shanghai Veterinary Research Institute - Chinese Academy of Agricultural Sciences, China
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.
Keywords :
toxiccophore , cytotoxicity mechanism , 2-propenyl moiety , quinocetone
