研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

开发具有潜在抗癌活性的多激酶抑制剂5-羟基苯并噻吩衍生物。

Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.

发表日期:2024
作者: Yara A Abd El-Rahman, Po-Jen Chen, Ahmed K ElHady, Shun-Hua Chen, Hsin-Chieh Lin, Dalia S El-Gamil, Youssef Aboushady, Ashraf H Abadi, Matthias Engel, Mohammad Abdel-Halim
来源: Cell Death & Disease

摘要:

目的:癌症的化学耐药性挑战了“一分子一靶点”的经典治疗策略。为了解决这个问题,提出了同时抑制各种癌症相关靶点的多靶点疗法。方法
Aim: Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed. Methods & results: We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines. Specifically, compound 16b, featuring a 5-hydroxybenzothiophene hydrazide scaffold, emerged as a potent inhibitor, displaying low IC50 values against key kinases and demonstrating significant anti-cancer effects, particularly against U87MG glioblastoma cells. It induced G2/M cell cycle arrest, apoptosis and inhibited cell migration by modulating apoptotic markers. Conclusion: 16b represents a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core.