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醇衍生物作为瘤微环境中的强效免疫调节剂

Alberto Pla-López¹, Miguel Carda¹, Eva Falomir¹

¹Inorganic and Organic Chemistry Department, University Jaume I, E-12071 Castellón, Spain.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

|November 17, 2023

概括

合成并测试了tetrazole衍生物的抗癌性质. 含氨酸的化合物显示出作为瘤微环境免疫调节剂的前景,而特定的和衍生物在HT-29癌细胞中诱导了亡.

科学领域:

药用化学医学化学
癌症生物学癌症生物学
免疫学免疫学免疫学

背景情况:

醇支架以其多样化的生物活动而闻名.
调节瘤微环境 (TME) 是癌症治疗的一个关键策略.
向编程死亡连接体1 (PD-L1),血管内皮生长因子受体2 (VEGFR-2),分化集群47 (CD-47) 和c-Myc在癌症治疗中至关重要.

研究的目的:

设计,合成和评估新型四醇衍生物的抗癌潜力.
为了比较电子捐赠 (氨基) 与电子接受 (亚) 组对醇衍生物的影响.
研究这些化合物对PD-L1,VEGFR-2,CD-47,c-Myc和TNF-α分泌的抑制作用.

主要方法:

合成27种含有四醇的化合物.
通过单一培养 (HT-29,A-549,MCF-7,HEK-293) 和共同培养 (HT-29/THP-1) 的测定来评估抗增殖活性.
对PD-L1,VEGFR-2,CD-47和c-Myc.进行抑制分析.
评估瘤亡因子-α (TNF-α) 的分泌.

主要成果:

衍生物 (23,24) 和衍生物 (26,27) 在HT-29癌细胞中诱导了亡.
含氨基组的化合物在TME中表现出显著的免疫调节作用.
几种化合物表现出对PD-L1,VEGFR-2,CD-47和c-Myc.的抑制活性.

结论:

醇衍生物,特别是那些含有氨基替代剂的衍生物,代表了一类有前途的TME免疫调节剂.
特定的基四醇具有直接的细胞毒性作用,诱导癌细胞的亡.
设计的四醇化合物具有作为多向抗癌疗法的潜力.

关键词:

氨基氨基是一种氨基氨基.反扩散活动的反扩散活动.细胞灭亡 (apoptosis) 是一种死亡的过程.这就是C-Mycc.这是一张CD-47的CD-47.在PD-L1中.这就是THP-1的特点.这就是TNF-α.泰特拉尔 (tetrazole) 是一种可以在VEGFR-2的基础上,

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