Mohammad A Khanfar, Ibrahim M Salman, Omar Z Ameer
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引用次数: 0
摘要
背景：成纤维细胞生长因子受体-1（FGFR-1）是一种酪氨酸激酶，也是治疗不同类型癌症的有效靶点：设计和合成新型噻唑类抗癌剂：方法：合成了一系列与结构可变的碱性头相连的 2-芳基-5-甲基噻唑类似物作为新型抗癌剂。对所开发的化合物进行了针对几种癌细胞系的细胞毒活性测试：结果：许多类似物对乳腺癌细胞株具有很强的抗增殖活性，对高转移性细胞株（MDA-MB-231）的效力更高。利用内部药效数据库进行的药效分析发现，FGFR-1 是活性类似物的分子靶标。对合成的化合物进行了生物测定，以确定其对 FGFR-1 的抑制活性：结论：与碱性头相连的 2-芳基-5-甲基噻唑是一种新型的 FGFR-1 ATP 竞争性抑制剂化学支架，对不同类型的癌症具有潜在的治疗活性。
Synthesis and Biological Evaluation of Thiazole-based Fibroblast Growth Factor Receptor-1 Inhibitors.
Background: The Fibroblast Growth Factor Receptor-1 (FGFR-1) is a tyrosine kinase and a validated target for the treatment of different cancer types.
Objective: Design and synthesis of novel thiazole-based analogues of anticancer agents.
Methods: Series of 2-aryl-5-methylthiazole analogues linked to structurally variable basic heads were synthesized as novel anticancer agents. Developed compounds were tested for their cytotoxic activities against several cancer cell lines.
Results: Many analogues exhibited strong antiproliferative activities against breast cancer cell lines, with higher potency towards the highly metastatic form (MDA-MB-231). Pharmacophoric profiling using an in-house pharmacophore database identified FGFR-1 as a molecular target of active analogues. Synthesized compounds were bioassayed for their FGFR-1 inhibitory activities and many hits exhibited IC50 values in the low micromolar to nanomolar range.
Conclusion: The 2-aryl-5-methylthiazole linked to a basic head is a novel chemical scaffold of ATP-competitive inhibitor of FGFR-1 with potential therapeutic activities against different types of cancer.
期刊介绍：
Formerly: Current Medicinal Chemistry - Anti-Cancer Agents.
Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents.
Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication.
Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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