N‐substituted hydroxynaphthalene imino‐oxindole derivatives as new class of PI3‐kinase inhibitor and breast cancer drug: Molecular validation and structure–activity relationship studies

N‐substituted hydroxynaphthalene imino‐oxindole derivatives (5a–g) were emerged as the inhibitors of the phosphoinositide 3‐kinase (PI3K), which is a crucial regulator of apoptosis or programmed cell death. Electron donor‐/acceptor‐substituted indole‐imine (5a–g) was achieved, and the structures were elucidated by FTIR, 1H NMR, 13C NMR and HRMS. Inhibition potency of PI3Ks was assessed by competitive ELISA. Subsequently, an anticancer activity against breast cancer (MCF‐7) cell lines was evaluated. In both activities, compounds 5c, 5d and 5f showed most potent activities. Percentage inhibition for anticancer activity was 78.22 ± 1.02 (5c) and 78.98 ± 1.08 (5f), and the IC50 was 2.02 ± 0.92 μm (5c) and 1.98 ± 0.18 μm (5f). Compounds 5a and 5g were found inactive for both activities, and rest all showed a moderate activity. To get more insight into the binding mode and inhibitor binding affinity, 5a–g were docked into the active site of PI3Ks p110α (PDB ID: 2ENQ). Results suggested that the hydrophobic interactions in the binding pockets of PI3Ks conquered affinity of the most favourable binding ligands (5c and 5f: inhibitory constant (ki) = 102.4 and 128.23 nm). The SAR studies demonstrate the efficiency of 5a–g as the PI3Ks precise inhibitors with the impending to treat various cancers. Imino‐oxindole derivatives (5a–g) were evaluated and found as efficient therapeutics against breast cancer.