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Bioorg Med Chem Lett. 2015 Aug 15;25(16):3120-4. doi: 10.1016/j.bmcl.2015.06.011. Epub 2015 Jun 11.

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

Author information

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.

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

PMID:
26099539
DOI:
10.1016/j.bmcl.2015.06.011
[Indexed for MEDLINE]

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