基于烯醇的支架用于破坏瘤微环境
Alberto Pla-López1, Paula Martínez-Colomina2, Laura Cañada-García3
1Departament de Química Inorgànica i Orgànica, Universitat Jaume I, E-12071 Castellón, Spain.
Bioorganic & medicinal chemistry
|October 20, 2023
概括
新的醇化合物显示出潜在的瘤微环境破坏者. 最有效的化合物减少了共同培养中的癌细胞生长和IL-6分泌,影响了关键瘤标.
科学领域:
- 药用化学 医学化学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 瘤微环境 (TME) 在癌症进展和免疫规避中发挥着关键作用.
- 针对TME组件为新型癌症疗法提供了一个有前途的战略.
- 醇衍生物是一种具有多种生物活性的化合物.
研究的目的:
- 合成和评估新型的烯醇,三醇和四醇作为潜在的TME破坏者.
- 评估这些化合物对各种癌症细胞系的抗增殖作用.
- 研究化合物对特定TME相关分子标和细胞过程的影响.
主要方法:
- 合成39个基醇,13个基醇和27个基醇.
- 对HT-29,A-549,MCF-7 (瘤) 和HEK-293 (非瘤) 细胞系进行抗增殖试验.
- 在HT-29细胞中评估PD-L1,CD-47,c-Myc和VEGFR-2表达.
- 与HT-29和THP-1单细胞进行共同培养研究,以评估抗增殖活性和IL-6分泌.
- 分别对HMEC-1和HEK-293细胞进行血管生成和血管生成模拟测试.
主要成果:
- 在环上含有氨基基团和环上含有素的化合物表现出显著的TME破坏活性.
- 最强效的化合物显著降低了HT-29细胞种群在与THP-1单细胞共同培养中.
- 这种化合物也显著降低了IL-6的分泌,对PD-L1,CD-47和c-Myc的表达有中度影响.
- 选择的化合物表现出抗血管性和抗血管性模仿效应.
结论:
- 新型醇衍生物显示出作为破坏瘤微环境的干扰剂的前景.
- 鉴定的化合物通过调节TME组件和细胞交叉声调节,表现出强大的抗癌作用.
- 对这些化合物的进一步研究可能会导致针对TME的新型癌症治疗药物的开发.
关键词:
血管新生的产生.反扩散活动的反扩散活动.这是一张CD-47的CD-47.在IL-6的研究中,IL-6被认为是IL-6的基因.在PD-L1中.泰特拉尔 (tetrazole) 是一种可以三醇是一种三醇.瘤微环境是一个微环境.在VEGFR-2的基础上,c-Myccc 的意思是我的更多相关视频
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