新型的英多尔-皮拉混合物作为潜在的布林向剂;合成,抗增殖评估和分子建模研究
Mohammed Hawash1,2, Sezen Guntekin Ergun3,4, Deniz Cansen Kahraman3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330, Ankara, Turkey.
Journal of molecular structure
|May 26, 2023
概括
新的印-3-皮拉-5-碳胺衍生物显示出强大的抗癌活性. 化合物18有效地向肝细胞癌 (HCC) 细胞,通过抑制素聚合和诱导亡.
科学领域:
- 药用化学 医学化学
- 癌症生物学 癌症生物学
- 分子药理学分子药理学
背景情况:
- 印度尔-3-皮拉-5-碳胺基架被探索为抗癌性质.
- 索拉芬尼是肝细胞癌 (HCC) 的基准向治疗方法.
研究的目的:
- 设计,合成和评估新型的印尔-3-皮拉尔-5-碳胺类类似物,用于抗增殖活性.
- 识别有力的抗癌药物,特别是针对肝细胞癌 (HCC).
主要方法:
- 合成印-3-皮拉-5-碳胺类同类物 (化合物10-29).
- 使用硫胺B测定对Huh7,MCF-7和HCT116癌细胞系进行评估的抗增殖活性.
- 对于化合物18进行了布林聚合抑制测定,流细胞计 (细胞循环停止和亡诱导),分子对接和量子力学计算.
主要成果:
- 几种类型的药物表现出与索拉费尼布相当或超过的抗癌活性.
- 化合物18表现出对HCC细胞系 (IC50:0.6-2.9微米) 的强烈活性和中度的氨酸聚合抑制 (IC50: 19微米).
- 化合物18诱导G2/M阶段细胞周期停止和HCC细胞的细胞死亡,得到对接和量子力学研究的支持.
结论:
- 印-3-皮拉-5-碳胺类类似物代表了一类有前途的抗癌药物.
- 化合物18是针对肝细胞癌的进一步开发的有力候选者,通过氨酸抑制和亡诱导起作用.
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