PDF(Pubmed)
Abstract：
A series of novel echinatin derivatives with 1,3,4-oxadiazole moieties were designed and synthesized. Most of the newly synthesized compounds exhibited moderate antiproliferative activity against the four cancer cell lines. Notably, Compound T4 demonstrated the most potent activity, with IC50 values ranging from 1.71 µM to 8.60 µM against the four cancer cell lines. Cell colony formation and wound healing assays demonstrated that T4 significantly inhibited cell proliferation and inhibited migration. We discovered that T4 exhibited moderate binding affinity with the c-KIT protein through reverse docking. The results were effectively validated through subsequent molecular docking and c-KIT enzyme activity assays. In addition, Western blot analysis revealed that T4 inhibits the phosphorylation of downstream proteins of c-KIT. The results provide valuable inspiration for exploring novel insights into the design of echinatin-related hybrids as well as their potential application as c-KIT inhibitors to enhance the efficacy of candidates.
摘要：
设计并合成了一系列具有1,3,4-恶二唑部分的新型棘突素衍生物。大多数新合成的化合物对四种癌细胞系表现出中等的抗增殖活性。值得注意的是,化合物T4表现出最有效的活性，对四种癌细胞系的IC50值范围为1.71µM至8.60µM。细胞集落形成和伤口愈合试验表明,T4显著抑制细胞增殖并抑制迁移。我们发现T4通过反向对接表现出与c-KIT蛋白的中等结合亲和力。该结果通过随后的分子对接和c-KIT酶活性测定得到有效验证。此外,Western印迹分析显示T4抑制c-KIT下游蛋白的磷酸化。该结果为探索与棘突素相关的杂种的设计及其作为c-KIT抑制剂的潜在应用以增强候选物的功效提供了有价值的启发。
