Molecular Substantiation and Drug Efficacy of Relatively High Molecular Weight S‐BINOLs; Appraised as Breast Cancer Medication and PI3Kinase Inhibitors

Relatively high molecular weight S‐BINOLs with substituted functional groups were synthesized, and structures were elucidated by FTIR, ¹H nuclear magnetic resonance, ¹³C nuclear magnetic resonance, and HRMS. As a preliminary step, the compounds were docked into the active site of phosphoinositide3‐kinase (PI3Kinase) (Protein Data Bank ID: 2IUG) that is a crucial regulator of apoptosis or programmed cell death. To ensure the PI3Kinase inhibition, because it was predicted as the most suitable bioactivity of these compounds, a competitive ELISA PI3Kinase inhibition study was carried out. Compounds 3 , 4a , 4b , and 6 were assessed for cytotoxicity/antiproliferative effects on MCF‐7 (breast cancer) and HCT116 (colon cancer) cell lines. In the docking studies, excellent binding affinities of 3 , 4a , 4b , and 6 (−11.36, −14.52, −14.86, and −21.76 kcal/mol, respectively) and the inhibitory constants (ki) (4.75 nM, 81.64 pM, 78.23 pM, and 14.24 pM, respectively) encouraged us to carry out anticancer studies further. Excellent inhibitory values were obtained in the range of 82–90% relative activity and IC₅₀ range of 5–12 nM. In the cytotoxicity, the relative inhibition activity was remarkably found high in MCF‐7 cell lines as 89.14% ( 6 ), 82.18% ( 4b ), 80.46% ( 3 ), and 74.78% ( 4a ) with the IC₅₀ range of 0.02–0.18 μM. No compounds were found inactive for the proposed activity in this study. The Structure Activity Relationship studies prove that compounds 3 , 4a , 4b , and 6 are specific PI3Kinase inhibitors with the competence to cure breast cancers.