Synthesis and Biological Evaluation of Novel Indole-2-one and 7-aza-2-oxindole Derivatives As Anti-inflammatory Agents

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2014 Nov 8

PMID 25378906

Citations 1

Authors

Gaozhi Chen

Lili Jiang

Lili Dong

Zhe Wang

Fengli Xu

Ting Ding

Lili Fu

Qilu Fang

Zhiguo Liu

Xiaoou Shan

Guang Liang

Affiliations

Soon will be listed here.

Abstract

Sepsis, a typically acute inflammatory disease, is the biggest cause of death in ICU (intensive care unit). Novel anti-inflammatory alternatives are still in urgent need. In this study, we designed and synthesized 30 indole-2-one and 7-aza-2-oxindole derivatives based on the skeleton of tenidap, and their anti-inflammatory activity was determined by evaluating the inhibitory potency against lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-α and interleukin (IL)-6 release in RAW264.7 macrophages. Quantitative SAR (structure-activity relationship) analysis revealed that a high molecular polarizability and low lipid/water partition coefficient (ALogP) in indole-2-one are beneficial for anti-inflammatory activity. Moreover, compounds 7i and 8e inhibited the expression of TNF-α, IL-6, COX-2, PGES, and iNOS in LPS-stimulated macrophages, and 7i exhibited a significant protection from LPS-induced septic death in mouse models. These data present a series of new indole-2-one compounds with potential therapeutic effects in acute inflammatory diseases.

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