Background: Spirocyclic indoline compounds widely exist in numerous natural products with good biological
activities and some drug molecules in many aspects. In recent years, it has 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 a set of novel 1'-H-spiro[indole-3,4'-piperidine] derivatives,
which were evaluated by preliminary bioactivity experiment in vitro and molecular docking.
Method: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different
substituents under alkaline condition to obtain its sulfonyl derivatives (B5-B10). We evaluated their antiproliferative
activities against A549, BEL-7402 and HeLa cells by MTT assay. We performed the CDOCKER module in Discovery Studio
2.5.5 software for molecular modeling of compound B5, and investigated the binding of compound B5 with the target
proteins from PDB database.
Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three
types of cells, in which compound B5 with chloride atom as electron-withdrawing substituent on a phenyl ring showed the
highest potency against BEL-7402 cells (IC50=30.03±0.43 μg/mL). By binging of the prominent bioactive compound B5 to
CDK, c-Met, EGFR protein crystals, The binding energy of B5 with these three types receptors are -44.3583 kcal/mol, -
38.3292 kcal/mol, -33.3653 kcal/mol respectively.
Conclusion: Six 1'-methylspiro[indoline-3,4'-piperidine] derivatives were synthesized and evaluated against BEL-7402, A-
549, HeLa cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking revealed that
B5 showed good affinity by the good fitting between B5 and these three targets with amino acid residues in active sites
which encourage us to conduct further evaluation such as the kinase experiment.