Sabbah, Dima A; Saada, Musaab; Khalaf, Reema Ab A; Bardaweel, Sanaa; Sweidan, Kamal; Al-Qirim, Tariq; Al-Zughier, Amani; Halim, Heba Abde A; Sheikha, Ghassan Ab A
description
The oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has made it an attractive target for anticancer drug design. In this work, we describe our efforts to optimize the lead PI3Kα inhibitor 2-hydroxy-1,2-diphenylethanone (benzoin). A series of 2-oxo-1,2-diphenylethyl benzoate analogs were identified as potential PI3Kα inhibitors. Docking studies confirmed that the aromatic interaction is mediating ligand/protein complex formation and identified Lys802 and Val851 as H-bonding key residues. Our biological data in human colon carcinoma HCT116 showed that the structure analogs inhibited cell proliferation and induced apoptosis.
