基于链接器的药法设计和半合成的拉布丹结合剂对多面性炎症点有活力
Sangeetha Mohan1,2, Lekshmy Krishnan1, Nithya Madhusoodanan1,2
1Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram 695 019, Kerala, India.
Journal of agricultural and food chemistry
|March 18, 2024
概括
来自Curcuma amada的新型植物化学物质显示出强大的抗炎作用. 化合物5f有效抑制了循环氧化酶-2 (COX-2) 并减少了关键的炎症介质,表明了治疗潜力.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 自然产品 自然产品
背景情况:
- 长时间的炎症与癌症和阿尔茨海默氏症等疾病有关.
- 过度的促炎媒介 (NO,TNF-α,IL-6,IL-1α) 和酶 (COX-2) 驱动不受控制的炎症.
- 降低这些介质的调节对于控制炎症和预防组织损伤至关重要.
研究的目的:
- 设计和合成具有抗炎潜力的新型植物化学实体 (NPCE).
- 评估NPCEs对COX-2和其他炎症媒介的抑制作用.
- 研究NPCEs抗炎活性背后的分子机制.
主要方法:
- 通过使用Curcuma amada中的labdane二甲基与芳香/异芳香碎片的基于链接器的分子杂交合成NPCEs.
- 在体外评估抗炎活性,包括抑制COX-2和减少NO,TNF-α,IL-6和IL-1α在LPS刺激的巨细胞中.
- 在基分子建模研究中,针对COX-2酶.
- 关于COX-2表达和NF-κB信号通路抑制的机制研究.
主要成果:
- 化合物5f表现出显著的COX-2抑制 (IC50 = 17.67 ± 0.89μM),表现优于标准药物印米他辛.
- 5f显著降低了LPS诱导的NO,TNF-α,IL-6和IL-1α水平.
- 机制性研究证实了剂量依赖的COX-2表达的抑制和通过NF-κB通路的抑制释放促炎性细胞因子.
结论:
- 拉布丹衍生物5f具有强大的抗炎性质.
- 5f有效调节关键的炎症媒介和通路.
- 化合物5f代表了开发新型抗炎疗法的有希望的领先候选人.
关键词:
在COX-2中,COX-2是最常见的.黄 (Curcuma amada) 是一种的植物.在IL-1α上.在IL-6的研究中,IL-6被认为是IL-6的基因.在 NF-κBB 中.这就是TNF-α.拉巴丹-合物 拉巴丹-合物更多相关视频
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