Deciphering the Anticancer Property of Fluorophenyl Spirooxindole Hybrid ‐ From Structural Elucidation to Quantum and Biological Studies

ABSTRACT A fluorinated spirooxindole‐based piperidine derivative was synthesized and structurally characterized. The molecular structure of the compound 1‐Methyl‐4‐(2‐fluorophenyl)pyrrolo‐(spiro[2.3″]oxindole)‐spiro[3.3’]‐5’‐(2‐fluorophenylmethylidene)‐1’‐ N ‐(propargyl)piperidin‐4’‐one was confirmed by SC‐XRD. In this compound, the pyrrole ring is in a twisted envelope conformation while the central piperidine ring adopts a half‐chair conformation. The intermolecular hydrogen bond interactions [N(2)–H(2A)…O(2)] and [C(20’B)–H(20’B)…F(1)] play an important role in reinforcing the lattice cohesion. Hirshfeld surface analysis correlated well with the crystallographic data, quantitatively confirming intermolecular interactions. The two‐dimensional fingerprint plots verified the contacts that contribute to the crystal packing(C···H/H…C (25.5%), H···H(52.2%), and H···F/F…H(10.4%)). Density Functional Theory (DFT) analysis quantifies the higher electronic stability of the molecule with a wide HOMO–LUMO energy gap (6.498 eV). Molecular docking studies of the title compound against the tyrosine kinase domain (PDB ID: 4L23) showed a strong binding affinity (−11.86 kcal mol − 1 ), compared to the standard drugs like letrozole. which was further corroborated by molecular docking simulations studies which demonstrated a stable protein ‐ligand complex formation over a long time period trajectory of 300 ns, which is further supported by MM‐PBSA free energy calculations. These integrated results from all the studies confirmed the inhibition potential of the fluorinated spirooxindole scaffold against breast cancer.