Abstract：
BACKGROUND: Non-small cell lung cancer (NSCLC) patients often benefit from EGFR inhibitors like gefitinib. However, drug resistance remains a significant challenge in treatment. The unique properties of 1,2,3-triazole, a nitrogen-based compound, hold promise as potential solutions due to its versatile structural attributes and diverse biological effects, including anticancer properties.
METHODS: Our synthesis process involved the huisgen cycloaddition chemical method, which generated diverse icotinib derivatives. We evaluated the anticancer capabilities of these derivatives against various cancer cell lines, with a specific focus on NSCLC cells that exhibit drug resistance. Additionally, we investigated the binding affinity of selected compounds, including 3l, towards wild-type EGFR using surface plasmon resonance (SPR) experiments.
RESULTS: Notably, icotinib derivatives such as derivative 3l demonstrated significant efficacy against different cancer cell lines, including those resistant to conventional therapies. Compound 3l exhibited potent activity with IC50 values below 10 μM against drug-resistant cells. SPR experiments revealed that 3l exhibited enhanced affinity towards wild-type EGFR compared to icotinib. Our research findings suggest that 3l acts as a compelling antagonist for the protein tyrosine kinase of EGFR (EGFR-PTK).
CONCLUSIONS: Icotinib derivative 3l, featuring a 1,2,3-triazole ring, demonstrates potent anticancer effects against drug-resistant NSCLC cells. Its enhanced binding affinity to EGFR and modulation of the EGFR-RAS-RAF-MAPK pathway position 3l as a promising candidate for the future development of anticancer drugs.
METHODS: Our synthesis process involved the huisgen cycloaddition chemical method, which generated diverse icotinib derivatives. We evaluated the anticancer capabilities of these derivatives against various cancer cell lines, with a specific focus on NSCLC cells that exhibit drug resistance. Additionally, we investigated the binding affinity of selected compounds, including 3l, towards wild-type EGFR using surface plasmon resonance (SPR) experiments.
RESULTS: Notably, icotinib derivatives such as derivative 3l demonstrated significant efficacy against different cancer cell lines, including those resistant to conventional therapies. Compound 3l exhibited potent activity with IC50 values below 10 μM against drug-resistant cells. SPR experiments revealed that 3l exhibited enhanced affinity towards wild-type EGFR compared to icotinib. Our research findings suggest that 3l acts as a compelling antagonist for the protein tyrosine kinase of EGFR (EGFR-PTK).
CONCLUSIONS: Icotinib derivative 3l, featuring a 1,2,3-triazole ring, demonstrates potent anticancer effects against drug-resistant NSCLC cells. Its enhanced binding affinity to EGFR and modulation of the EGFR-RAS-RAF-MAPK pathway position 3l as a promising candidate for the future development of anticancer drugs.
摘要：
背景：非小细胞肺癌（NSCLC）患者通常受益于吉非替尼等EGFR抑制剂。然而,耐药性仍然是治疗中的重大挑战。1,2,3-三唑的独特性质,基于氮的化合物，由于其多功能的结构属性和多样化的生物效应，有望成为潜在的解决方案，包括抗癌特性。
方法：我们的合成过程涉及Huisgen环加成化学法，产生了不同的埃克替尼衍生物。我们评估了这些衍生物对各种癌细胞系的抗癌能力，特别关注表现出耐药性的NSCLC细胞。此外,我们研究了所选化合物的结合亲和力，包括3L，使用表面等离子体共振（SPR）实验对野生型EGFR。
结果：值得注意的是，埃克替尼衍生物如衍生物3l证明了对不同癌细胞系的显著功效，包括那些对常规疗法有抵抗力的。化合物3l对耐药细胞表现出有效的活性,IC50值低于10μM。SPR实验显示,与埃克替尼相比,3l对野生型EGFR表现出增强的亲和力。我们的研究结果表明,3l充当EGFR的蛋白酪氨酸激酶(EGFR-PTK)的引人注目的拮抗剂。
结论：埃克替尼衍生物3l，有一个1,2,3-三唑环,证明了对耐药NSCLC细胞的有效抗癌作用。其增强的对EGFR的结合亲和力和EGFR-RAS-RAF-MAPK通路位置3l的调节作为抗癌药物未来发展的有希望的候选物。
方法：我们的合成过程涉及Huisgen环加成化学法，产生了不同的埃克替尼衍生物。我们评估了这些衍生物对各种癌细胞系的抗癌能力，特别关注表现出耐药性的NSCLC细胞。此外,我们研究了所选化合物的结合亲和力，包括3L，使用表面等离子体共振（SPR）实验对野生型EGFR。
结果：值得注意的是，埃克替尼衍生物如衍生物3l证明了对不同癌细胞系的显著功效，包括那些对常规疗法有抵抗力的。化合物3l对耐药细胞表现出有效的活性,IC50值低于10μM。SPR实验显示,与埃克替尼相比,3l对野生型EGFR表现出增强的亲和力。我们的研究结果表明,3l充当EGFR的蛋白酪氨酸激酶(EGFR-PTK)的引人注目的拮抗剂。
结论：埃克替尼衍生物3l，有一个1,2,3-三唑环,证明了对耐药NSCLC细胞的有效抗癌作用。其增强的对EGFR的结合亲和力和EGFR-RAS-RAF-MAPK通路位置3l的调节作为抗癌药物未来发展的有希望的候选物。
