含有双循环松骨的酸作为表观遗传和代谢调节剂:协同作用剂克服西斯普拉丁耐药性
Yulia Aleksandrova1, Aldar Munkuev2, Evgenii Mozhaitsev2
1Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Severnij Pr. 1, 142432 Chernogolovka, Russia.
Cancers
|October 28, 2023
概括
新的胺酸可以对抗癌症中的化疗耐药性. 化合物18c,具有双循环皮南,与西斯普拉丁协同作用,抑制组织激素脱乙酶1和糖解,以消除瘤细胞.
科学领域:
- 药用化学 医学化学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 多药耐药性 (MDR) 是癌症化疗的一个主要挑战,需要新的治疗策略.
- 新生细胞采用多种机制来抵抗抗瘤剂,突出强调迫切需要有效的解决方案.
- 酸是生物活性化合物的一类,具有潜在的药理学应用.
研究的目的:
- 合成新的含有p替代的肉酸核心和双循环松碎片的酸.
- 确定可以克服癌症多药性耐药性的化合物.
- 评估这些化合物的协同效应与现有的化疗法,如西斯.
主要方法:
- 来自 (-) - 米尔醇, (+) - 米尔醇和 (-) - 诺波尔的胺酸的合成.
- 合成化合物的抗癌疗效测试.
- 评估与西斯的协同效应.
- 调查潜在的作用机制,包括基因素脱乙酶1和抑制糖解功能.
主要成果:
- 成功合成了几种含有双循环松酸碎片的素酸.
- 化合物18c,含有 (-) - - 诺波尔衍生的上限组,显示出显著的前景.
- 化合物18c与思柏林协同作用,增强其抗癌作用并克服思柏林耐药性.
- 抑制基因素脱乙酶1和糖溶性功能与18c化合物所观察到的效应有关.
结论:
- 具有双循环皮纳骨架的胺酸代表了癌症治疗的有前途的治疗方法.
- 化合物18c显示出消除瘤细胞和克服恶性瘤中耐药性的潜力.
- 向基因素脱乙酶1和糖溶性通路可能是克服MDR的关键机制.
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