Background: Spirocyclic indoline compounds widely exist in numerous natural products and synthetic molecules with significant biological activities. In recent years, these kinds of compounds have attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry.

Objective: In this study, we focused on designing and synthesizing novel 1'-methylspiro[indoline- 3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking.

Materials and Methods: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cell lines by MTT assay. We performed the CDOCKER module in Accelrys Discovery Studio 2.5.5 for molecular docking of compound B5, and investigated the binding modes of compound B5 with three different target proteins.

Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cell lines, in which compound B5 with chloride atom as electronwithdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cell lines (IC₅₀=30.03±0.43 μg/mL). The results of molecular docking showed that the binding energies of the prominent bioactive compound B5 with CDK, c-Met, and EGFR protein crystals are -44.3583 kcal/mol, -38.3292 kcal/mol, -33.3653 kcal/mol, respectively.

Conclusion: 1'-methylspiro[indoline-3,4'-piperidine] and its six derivatives were synthesized and evaluated against BEL-7402, A 549, and Hela cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking assays revealed that B5 as a ligand showed strong affinity and appropriate binding pose on the amino acid residues in active sites of the tested targets, which encourage us to conduct further evaluation such as the kinase experiment.

背景：螺环二氢吲哚化合物广泛存在于众多具有显着生物活性的天然产物和合成分子中。近年来，这些化合物作为有效的抗肿瘤药物在药理和化学领域受到广泛关注。

目的：在本研究中，我们重点设计和合成了新型 1'-甲基螺[二氢吲哚-3,4'-哌啶] 衍生物，并通过体外初步生物活性实验和分子对接对其进行了评估。

材料与方法：关键中间体1'-甲基螺[indoline-3,4'-哌啶]（B4）与不同取代基的苯磺酰氯在碱性条件下反应得到其衍生物（B5-B10）。我们通过 MTT 测定评估了它们对 A549、BEL-7402 和 HeLa 细胞系的抗增殖活性。我们在 Accelrys Discovery Studio 2.5.5 中执行 CDOCKER 模块以进行化合物 B5 的分子对接，并研究了化合物 B5 与三种不同靶蛋白的结合模式。

结果：结果表明化合物B4-B10对上述三种细胞系均表现出良好的抗增殖活性，其中苯环上以氯原子为吸电子取代基的化合物B5对BEL-7402细胞系的抗增殖活性最高（IC ₅₀ =30.03±0.43 μg/mL)。分子对接结果表明，突出的生物活性化合物B5与CDK、c-Met和EGFR蛋白晶体的结合能分别为-44.3583 kcal/mol、-38.3292 kcal/mol、-33.3653 kcal/mol。

结论：合成了 1'-甲基螺[indoline-3,4'-哌啶] 及其六种衍生物，并针对 BEL-7402、A 549 和 Hela 细胞系进行了评估。化合物 B5 显示出对 BEL-7402 细胞系的显着抑制。分子对接分析表明，B5 作为配体对测试靶标活性位点的氨基酸残基显示出很强的亲和力和适当的结合姿势，这鼓励我们进行进一步的评估，例如激酶实验。