Sabbah, Dima A; Al-Azaideh, Bara'a A; Talib, Wamidh H; Hajjo, Rima; Sweidan, Kamal; Al-Zuheiri, Aya M; Sheikha, Ghassan Ab A; Shraim, Sawsan
description
Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new '-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (H and C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the -tailored derivatives [-NO () and -CF ()] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives and exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of -substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue.
