<b>Water Mediated Synthesis and Anticancer Evaluation of Oxindole-embedded Chalcone Hybrids: Insights from Computational Studies and A549 Cell Line Assay</b>

This study presents a novel water-mediated synthesis method for oxindole functionalized chalcone derivatives, which have various therapeutic applications, particularly in cancer treatment. The newly synthesized compounds were evaluated in vitro against the A549 and MDA-MB-231 cell lines, revealing that compounds 3d, 3g, 3a, and 3c were the most effective at targeting A549 lung cancer cells, with IC₅₀ values ranging from 8.85 to 13.87 μM. Additionally, docking experiments were conducted to investigate the affinities and interactions of these derivatives with the 6NEC protein, a key player in cancer pathways, to better understand their potential molecular mechanisms of action. Molecular dynamics simulations illustrated conformational changes during biomolecular interactions and confirmed that the compounds maintain structural stability, as indicated by Root Mean Square Deviation (RMSD) values consistently below 2Å. Furthermore, computational studies have validated the structural stability and mode of action of these substances, highlighting their potential for further development as cancer therapeutics.本研究报道了一种全新的水介导合成方法，用于制备羟吲哚（oxindole）功能化查尔酮（chalcone）衍生物——此类化合物具备多种治疗用途，尤其在癌症治疗领域应用前景广阔。本研究对新合成的化合物开展了针对A549与MDA-MB-231细胞系的体外活性评价，结果显示化合物3d、3g、3a及3c对A549肺癌细胞的抑制活性最为突出，其半最大效应浓度（IC₅₀）值介于8.85至13.87 μM之间。此外，本研究通过分子对接实验，探究了此类衍生物与癌症通路关键靶点6NEC蛋白的结合亲和力与相互作用模式，以深入阐明其潜在的分子作用机制。分子动力学模拟结果展示了生物分子相互作用过程中的构象变化，并通过均方根偏差（Root Mean Square Deviation，简称RMSD）值始终低于2埃的结果，证实了此类化合物具备良好的结构稳定性。进一步而言，计算生物学研究验证了此类化合物的结构稳定性与作用模式，凸显了其作为癌症治疗药物进一步开发的潜力。