Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, India.
Department of Pharmaceutical Sciences, HNB Garhwal University, Srinagar, India.
Assay Drug Dev Technol. 2023 Jul;21(5):222-233. doi: 10.1089/adt.2022.120. Epub 2023 Jul 12.
A series of isatin-based fused heterocycles were designed, synthesized, and evaluated for anticancer activity against four cancer cell lines: MCF-7, MDA-MB-231, A549, and HL-60. Among them, Q and T were found to be potent anticancer agents. Furthermore, two compounds Q and T were selected for epidermal growth factor receptor (EGFR) inhibitory activity. Two compounds Q and T were found to be most potent EGFR inhibitors with IC of 0.22 ± 0.10 and 0.19 ± 0.07 μM. The EGFR inhibitory activity of standard drug erlotinib was 0.08 ± 0.02 μM. Structural Activity Relationship studies showed that electronegative atoms were necessary for EGFR inhibitory potential. Finally, molecular docking studies were carried out to check the binding pattern of synthesized derivatives with the adenosine triphosphate (ATP) binding site of EGFR and results revealed that compounds Q (-9.2 kcal/mol) and T (-8.9 kcal/mol) exhibited better binding affinity than reference drug erlotinib (-7.3 kcal/mol).
设计、合成了一系列基于靛红的融合杂环化合物，并对它们在四种癌细胞系（MCF-7、MDA-MB-231、A549 和 HL-60）中的抗癌活性进行了评估。其中，化合物 Q 和 T 被发现具有很强的抗癌活性。此外，选择了两种化合物 Q 和 T 进行表皮生长因子受体（EGFR）抑制活性研究。结果发现，两种化合物 Q 和 T 是最有效的 EGFR 抑制剂，其 IC 分别为 0.22±0.10 和 0.19±0.07μM。标准药物厄洛替尼的 EGFR 抑制活性为 0.08±0.02μM。构效关系研究表明，EGFR 抑制潜力需要带负电荷的原子。最后，进行了分子对接研究，以检查合成衍生物与 EGFR 的三磷酸腺苷（ATP）结合位点的结合模式，结果表明化合物 Q（-9.2 kcal/mol）和 T（-8.9 kcal/mol）与参考药物厄洛替尼（-7.3 kcal/mol）相比，表现出更好的结合亲和力。
