开发新的抗癌类硫胺作为EGFR/碳酸无水酶双抑制剂的新型抗癌药物
Ibrahim H Eissa1, Hazem Elkady1, Walid E Elgammal2
1Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
新的硫胺衍生物显示出作为表皮生长因子受体 (EGFR) 和碳酸酶IX (CA-IX) 的双重抑制剂的潜力,用于选择性抗癌疗法.
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:
- 癌细胞经常过度表达表皮生长因子受体 (EGFR) 和碳酸无水酶IX (CA-IX).
- 针对EGFR和CA-IX同时提供了选择性抗癌药物开发的潜在策略.
- 提亚醇-硫胺基支架正在被探索,因为它们具有作为双重抑制剂的潜力.
研究的目的:
- 合成新型硫胺衍生物作为EGFR和CA-IX的双抑制剂.
- 评估合成的化合物对针对乳腺癌细胞系的选择性抗癌活性.
- 研究其作用机制,包括诱导细胞亡和细胞循环效应.
主要方法:
- 提亚醇-硫胺衍生物的合成.
- 在体外细胞毒性测定对MDA-MB-231,MCF-7和Vero细胞系.
- 对EGFR和CA-IX的酶抑制试验.
- 通过基因表达 (BAX/Bcl-2,caspases) 和流细胞测量来评估亡.
- 分子对接,分子动力学模拟,DFT计算和in silico ADMET预测.
主要成果:
- 化合物14对乳腺癌细胞 (MDA-MB-231,MCF-7) 具有强烈的细胞毒性,对正常Vero细胞具有很高的选择性.
- 化合物14有效抑制了EGFR和CA-IX酶,表现优于参考药物.
- 诱导了亡,其证据是BAX/Bcl-2比率的增加,酶激活和G1阶段细胞循环停止.
- 计算研究证实了稳定的结合相互作用和有利的药理动力学特性.
结论:
- 化合物14是一种有前途的双重EGFR/CA-IX抑制剂,具有选择性抗癌特性.
- 这些发现支持对化合物14在体内抗癌功效的进一步研究.
- 提亚醇-硫胺衍生物是开发向癌症治疗的可行类别.
更多相关视频
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
相关概念视频
Targeted Cancer Therapies
There are several types of targeted therapies against...
Mitogens and the Cell Cycle
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Inhibition of Cdk Activity
