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  3. A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies

A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies

  • Eur J Med Chem. 2024 Apr 15:270:116376. doi: 10.1016/j.ejmech.2024.116376.
Maryam Akhtar 1,  Luhao Lai 2,  Ting Tian 1,  Xu Zhang 1,  Hao Cheng 1,  Li Lin 3
Affiliations

Affiliations

  • 1 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
  • 2 Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, 272067, China.
  • 3 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. Electronic address: linli@lzu.edu.cn.
PMID: 38569433 DOI: 10.1016/j.ejmech.2024.116376
Abstract

A variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated for their anti-inflammatory activity in-vitro and in-vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE2 inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 Enzyme at 5 μM via ELISA experiment. Compound L-37 (1 μM) also inhibited the PGF1 production as well as the expression of COX-1, but displayed weak inhibition activity towards the Leukotrienes (LT) and Thromboxane-B2 (TXB-2) production. However, the expression of 5-LOX was significantly inhibited by compound L-39 at 5 μM. Xylene-induced ear edema model was explored for in-vivo anti-inflammatory evaluation, compound L-37 showed similar inhibitory activity compared with celecoxib, approximately 80% at 50 mg/kg dosage. Every outcome showed that the newly synthesized compounds can effectively inhibit inflammation.

Keywords

Anti-inflammatory; Celecoxib; Leukotriene; Nitric oxide; γ-hydroxy propiolate esters.

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