2. Academic Validation
  3. Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα)

Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα)

  • Bioorg Med Chem Lett. 2015 Aug 15;25(16):3120-4. doi: 10.1016/j.bmcl.2015.06.011.
Dima A Sabbah 1,  Musaab Saada 2,  Reema Abu Khalaf 2,  Sanaa Bardaweel 3,  Kamal Sweidan 4,  Tariq Al-Qirim 2,  Amani Al-Zughier 2,  Heba Abdel Halim 5,  Ghassan Abu Sheikha 2
Affiliations

Affiliations

  • 1 Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan. Electronic address: dima_sabbah@yahoo.com.
  • 2 Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan.
  • 3 Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan.
  • 4 Department of Chemistry, The University of Jordan, Amman 11942, Jordan.
  • 5 Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman, Jordan.
PMID: 26099539 DOI: 10.1016/j.bmcl.2015.06.011
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.

Keywords

Benzoin; Cancer; Docking; HCT116; PI3Kα.

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