Identification of Linomide Derivatives as Potential Anticancer Therapeutics using Molecular Docking Studies

12 analogs bearing a structural similarity to Linomide, a bonafide anticancer agent were synthesized wherein cyclization of substituted dianilides rendered 4-hydroxyquinolin-2(1H)-ones that were subjected to a Mannich reaction to yield 4-hydroxy-3-(substituted-1-ylmethyl) quinolin-2(1H)-one analogs. Characterization was performed using IR, H-1 nuclear magnetic resonance and C-13 NMR spectral analysis. Subsequently, in vitro anticancer studies revealed that Compound 4b showed maximum cytotoxicity with IC50 values of 1.539 mu M/ml and 1.732 mu M/ml against A549 and K562 cell lines respectively. This, however, is lower in comparison with standard Paclitaxel (IC50 values of 0.3 mu M/ml for both cell lines). Surprisingly, docking studies at the active site of EGFRK revealed Compound 4b possessed a MolDock Score of -110.2253 that is highly comparable to the standard 4-anilinoquinazoline (MolDock Score of -112.04). Our computational and biological data thus provides an insight on the cytotoxicity of these derivatives and warrants future research that can possibly lead to the development of potent anticancer therapeutics.

Automated summary

A series of compounds similar to the anticancer agent Linomide were synthesized and evaluated for their anticancer activity. Compound 4b showed high cytotoxicity, but lower than the standard drug Paclitaxel. Docking studies revealed that Compound 4b had good binding affinity at the active site of EGFRK.