Chinese Journal of Organic Chemistry >
Design, Synthesis and Anti-inflammatory Activity of Azulene Derivatives Containing Benzimidazole Unit
Received date: 2023-02-09
Revised date: 2023-04-12
Online published: 2023-05-23
Supported by
National Natural Science Foundation of China(22075310)
Benzimidazole (BI) unit exists in many bioactive compounds and has attracted more and more attention in the field of drug synthesis. Azulene derivatives are natural products obtained from medicinal plants, which have the characteristics of anti-inflammatory, antioxidant, and low toxicity. Using azulene derivatives and BI as raw materials, fourteen azulene derivatives that contain benzimidazole unit were synthesized by using Buchwald-Hartwig coupling strategy. Then their anti-inflammatory activity and structure-activity relationship were studied. The results showed that these compounds can effectively inhibit the production of NO in lipopolysaccharide (LPS) induced macrophages and have higher anti-inflammatory activity than sodium guaiazulene sulfonate (GAS-Na). Among them, three derivatives were screened with low toxicity and high anti-inflammatory activity, and they can inhibit the release of LPS-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner by enzyme-linked immunosorbent assay (ELISA). The results show that 1-guaiaculene benzimidazole (GABI-1) has high anti-inflammatory activity (the inhibitory rate of NO was 33.69% at the doses of 20 μmol/L) and low cytotoxicity, which is expected to become a candidate molecule for new anti-inflammatory drugs.
Mengjia Xiao , Xike Gao . Design, Synthesis and Anti-inflammatory Activity of Azulene Derivatives Containing Benzimidazole Unit[J]. Chinese Journal of Organic Chemistry, 2023 , 43(9) : 3246 -3256 . DOI: 10.6023/cjoc202302007
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