来自Nigrospora sphaerica的新索类同类及其对PD-1/PD-L1相互作用的抑制活性
Qi-Xuan Kuang1, Yu-Qing Huang1, Yan-Qiu Ruan2
1TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, People's Republic of China.
Bioorganic chemistry
|October 25, 2024
概括
来自Nigrospora sphaerica的天然化合物,包括nigrophenone A-D和nigropyrrolidinone,通过抑制PD-1/PD-L1相互作用和调节T细胞反应,显示出癌症免疫疗法的潜力.
科学领域:
- 自然产品 化学 化学
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- PD-1/PD-L1通路是癌症免疫治疗中的关键目标.
- 识别调节这种途径的新型小分子具有重大意义.
- 尼格洛斯波拉球菌 (Nigrospora sphaerica) 是一种已知产生生物活性化合物的真菌物种.
研究的目的:
- 从Nigrospora sphaerica中分离和描述新的化合物.
- 评估这些化合物对PD-1/PD-L1相互作用的抑制潜力.
- 研究最有前途的化合物的免疫调节和抗癌作用.
主要方法:
- 使用色谱和光谱技术对自然产品进行隔离和结构阐明.
- 表面等离子体共振 (SPR) 和ELISA测定量化结合亲缘关系和PD-1/PD-L1相互作用的抑制.
- 在体外测试以评估抗癌活性,T细胞激活,细胞因子分泌和途径调节.
主要成果:
- 他们分离了四种新的类药物 (nigrophenone A-D) 和一种pyrrolidinone类药物 (nigropyrrolidinone),以及13种已知的化合物.
- 化合物6,10,15和18表明抑制PD-1/PD-L1相互作用.
- 化合物6通过增强T细胞激活,上调PD-1表达,增加IFN-γ和IL-2分泌,抑制瘤细胞增殖和调节PI3K/Akt通路,显示出显著的体外抗癌作用.
结论:
- 从Nigrospora sphaerica中分离出来的天然产品具有抑制PD-1/PD-L1相互作用的能力.
- 化合物6显示出有前途的抗癌性质和免疫调节作用,需要对癌症免疫治疗应用进行进一步的研究.
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