Discovery and Evaluation of Novel Synthetic 5-alkyl-4-oxo-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoxaline-1-carbox-amide Derivatives As Anti-inflammatory Agents

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2019 Nov 12

PMID 31707866

Citations 4

Authors

Qing-Kun Shen

Guo-Hua Gong

Gao- Li

Mei- Jin

Li-Hua Cao

Zhe-Shan Quan

Affiliations

Soon will be listed here.

Abstract

To develop novel anti-inflammatory agents, a series of 5-alkyl-4-oxo-4,5-dihydro-[1, 2, 4]triazolo[4,3-a]quinoxaline-1-carboxamide derivatives were designed, synthesised, and evaluated for anti-inflammatory effects using RAW264.7 cells. Structures of the synthesised compounds were determined using H NMR, C NMR, and HRMS. All the compounds were screened for anti-inflammatory activity based on their inhibitory effects against LPS-induced NO release. Among them, 5-(3,4,5-trimethoxybenzyl)-4-oxo-4,5-dihydro-[1, 2, 4]triazolo[4,3-a]quinoxaline-1-carboxamide () showed the highest anti-inflammatory activity and inhibited NO release more potently than the lead compound . Further studies revealed that compound reduced the levels of NO, TNF-α, and IL-6, and that its anti-inflammatory activity involves the inhibition of COX-2 and iNOS and downregulation of the mitogen-activated protein kinases (MAPK) signal pathway. Notably, compound displayed more prominent anti-inflammatory activity than and the positive control ibuprofen in the acute inflammatory model. Overall, these findings indicate that compound is a therapeutic candidate for the treatment of inflammation.

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