Journal: Journal of Pharmacy Research

Article Id: JPRS-PC-00001614
Title: Design and synthesis of acridone-4-carboximide derivatives and their cytotoxic studies in cancer cells
Category: Pharmaceutical Chemistry
Section: Research Article
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    In search of developing potent cytotoxic molecules we have designed and synthesized novel scaffold by linking amines to acridone moiety. Novel acridone-4-carboximide derivatives were evaluated for their cytotoxic potentials against drug sensitive, resistant breast cancer cell lines (MCF7/wt, MCF7/mr and MCF7/dx) by using SRB assay. Moreover, Protein ligand interactions of acridone-4-carboxamide derivatives with P-glycoprotein was performed.  Compound 1 and 2 have shown relatively potent cytotoxic activity among the derivatives against sensitive, resistant cell lines. Further, compound 8 has shown good cytoxicity against sensitive cells, but it has poor activity in resistant cells. Perhaps, these derivatives were substrate for MDR pumps P-gp and BCRP. The predicted dock score was in the range of -10.48 to -4.71 attributed for compound 1 and 5 respectively. Protein residues such as TYR953, LEU339 and TYR310 were the major contributors for the H-bonding with docked ligands. Compound 1 showed 2 H-bonds, one each with TYR953, and TYR310 with a bond distance of 2.33Å, and 1.81Å respectively. Hydrogen bonds with both the residues were formed with 2 carbonyl oxygen. Additionally, dominant hydrophobic interactions were formed each between a phenyl ring of acridone nucleus and PHE983, toluene nucleus and PHE72 an TYR953.

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    Author(s) Name:

    M. Amareswararao1, Y. Rajesh Babu2, V.V.S. Rajendra Prasad 3*

    Affiliation(s) Name:

    1Clinical Research Department, Emcure Pharmaceuticals Ltd., Pune, India
    2Department of Pharmaceutical Chemistry, Gland Institute of Pharmaceutical Sciences, Narsapur,India
    3Medicinal Chemistry Research Division, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, India.

    *Corresponding author.
    Dr. V.V.S. Rajendra Prasad
    Professor,
    Medicinal Chemistry Research Division,
    Vishnu Institute of Pharmaceutical Education and Research,
    Narsapur-502313, India

    Received on:19-08-2016; Revised  on:  16-09-2016; Accepted on: 05-10-2016   

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    Author:

    M. Amareswararao1, Y. Rajesh Babu2, V.V.S. Rajendra Prasad 3*

    Title:Design and synthesis of acridone-4-carboximide derivatives and their cytotoxic studies in cancer cells
    Journal:Journal of Pharmacy Research
    Vol(issue):10 (October)
    Year:2016
    Page No: (628-634)
  • Experimental Methods Keywords

    Methodology:Design ,synthesis, cytotoxic studies
    Research Materials:acridone-4-carboximide derivatives

Keywords

Acridone SRB assay Breast cancer MCF7 Multidrug Resistance.

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