Discovery of Spirochromanone‐Based Molecular Hybrids as Promising Anticancer Leads: An Integrated Experimental and Theoretical Study

Cancer remains one of the leading causes of mortality worldwide, emphasizing the urgent need for the discovery of novel and selective chemotherapeutic agents. In this study, a new series of spirochromanone‐based molecular hybrids was rationally designed and synthesized to explore their potential as anticancer agents. The synthesized compounds were fully characterized by spectroscopic techniques including NMR and LCMS. The in vitro cytotoxic evaluation of the synthesized hybrids against a panel of human cancer cell lines (A549, HCT116, U2OS, Jurkat, CCRF‐CEM, MOLT‐4, RAMOS, K562, MRC‐5, and BJ cell lines) were assessed. Among all the compounds, 6b , 6c , 6g , 6h , and 6j have been displayed promising inhibition against RAMOS cell lines with an IC 50 range of 1.11–1.47 µM, respectively. In addition, compounds 6c , 6j , 6b , and 6f have been found to have potential inhibition against CCRF‐CEM cell lines with an IC 50 range of 7.71–13.55 µM. Furthermore, molecular docking studies were performed to explore the possible binding modes of the designed compounds within the active sites of ITK and BTK as a preliminary computational assessment. In silico ADMET analysis further supported the drug‐like nature and acceptable pharmacokinetic profiles of the active hybrids.