相关实验视频

Updated: Jun 27, 2025

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

针对白血病的新型瓜尼丁衍生物作为选择性Src/Abl双抑制剂:设计,合成和抗增殖活性

Amr H Moustafa¹, Asmaa M AboulMagd², Ali M Ali³

¹Faculty of Science, King Salman International University, Ras Sudr, Sinai 46612, Egypt; Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt.

Bioorganic chemistry

|April 30, 2024

概括

新的硫胺衍生物被合成为双 Src/Abl 抑制剂. 化合物3b对HL-60白血病细胞表现出强大的抗癌活性,选择性抑制Src/Abl激酶.

科学领域:

药用化学医学化学
分子生物学分子生物学
生物化学生物化学

背景情况:

Src 和 Abl 激酶是癌症治疗中的关键点.
开发具有强度和选择性的新兴抑制剂是一个持续的挑战.

研究的目的:

设计和合成新的硫胺衍生物作为双 Src/Abl 抑制剂.
评估这些化合物的抗癌活性和对癌细胞系和激酶的选择性.

主要方法:

合成N-(pyrimidin-2-yl) cyanamides衍生物的合成.
使用光谱数据 (IR,NMR) 和元素分析进行结构确认.
对NCI 60癌细胞系和一组铁酶激酶 (EGFR,VEGFR-2,B-raf,ERK,CK1,p38-MAPK,Src,Abl) 的查.
细胞周期分析和细胞亡测定.
分子对接研究和物理化学性质预测.

主要成果:

化合物3b对HL-60白血病细胞表现出强烈的抗增殖活性 (IC50 0.018 μM诺莫克西亚,0.001 μM缺氧).
化合物3b选择性抑制了Src/Abl激酶 (Src的IC50为0.25μM,Abl的IC50为0.08μM),其强度高于其他测试的激酶.
在HL-60细胞中观察到细胞循环停止和亡诱导的3b化合物,这表明通过Src/Abl抑制具有抗增殖作用.

结论:

合成的硫胺衍生物,特别是化合物3b,显示出作为癌症治疗的双Src/Abl抑制剂的显著潜力.
化合物3b的选择性和强烈活性需要进一步研究其治疗应用.

关键词:

反扩散活动的反扩散活动.细胞灭亡 (apoptosis) 是一种死亡的过程.这是一种二替代的关尼丁.在HL-60细胞系中.氧气过低是因为缺氧.Src / Abl 抑制活动的抑制活性.

更多相关视频

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

Published on: April 27, 2017

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Published on: September 9, 2016

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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...

Drugs that Destabilize Microtubules

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...