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, 1 H nuclear magnetic resonance, 13 C 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 IC 50 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 IC 50 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.