Design and Synthesis of Novel Spiro [Chromane‐2,4′‐Piperidin]‐4‐One Derivatives: Anti‐Proliferative Investigation and Molecular Docking Studies

Abstract Chemists around the globe are extensively working for remedial solutions to cancer, one of the greatest health hazards. We have synthesized twenty‐three novel spiro [chromane‐2,4′‐piperidin]‐ 4 ‐one derivatives ( KBS and KMS series of analogues) as part of our ongoing research to combat this deadly disease, and confirmed their structures using 1 H NMR, 13 C NMR, HRMS, and FT‐IR. Furthermore, we employed single‐crystal XRD to identify the compound structures of KBS4 and KMS10 . We have tested the compounds on the cell line such as MCF‐7; U87‐MG; SCC‐25; and HEK‐293T, via WST‐1 assay. Eight compounds showed IC 50 values ranging 3.9–10 μM; against the cell line MCF‐7. The best compounds of all were KMS9 (IC 50 =3.83 μM), KMS5 (IC 50 =4.14 μM), and KBS8 (IC 50 =8.24 μM), which promoted apoptosis in MCF‐7 cells. KMS5 and KMS9 compounds showed G1 cell cycle arrest, while compound KBS8 showed G2 cell cycle arrest. Insilco ADME studies were carried out. Molecular docking and dynamics experiments showed how KMS5 , KMS9 , and KBS8 bind to the active region of the EGFR family – a group of receptor tyrosine kinase (RTK) proteins (PDB ID: 7JXP, 2.16 Å) . Further structural modifications of the KMS5, KMS9 , and KBS8 may improve their activity against breast cancer.