title: Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα).
abstract: 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.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan. Electronic address: dima_sabbah@yahoo.com.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Sabbah
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan.
authors.forename: Musaab
authors.initials: M
authors.lastname: Saada
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan.
authors.forename: Reema Abu
authors.initials: RA
authors.lastname: Khalaf
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Bardaweel
authors.affiliation: Department of Chemistry, The University of Jordan, Amman 11942, Jordan.
authors.forename: Kamal
authors.initials: K
authors.lastname: Sweidan
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan.
authors.forename: Tariq
authors.initials: T
authors.lastname: Al-Qirim
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan.
authors.forename: Amani
authors.initials: A
authors.lastname: Al-Zughier
authors.affiliation: Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman, Jordan.
authors.forename: Heba Abdel
authors.initials: HA
authors.lastname: Halim
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan.
authors.forename: Ghassan Abu
authors.initials: GA
authors.lastname: Sheikha
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001573:Benzoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D045325:HCT116 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary
chemical_list: D000970:Antineoplastic Agents; D001573:Benzoin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors
keywords: Benzoin; Cancer; Docking; HCT116; PI3Kα