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Abstract

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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	JPR Solutions

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