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....
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Veröffentlicht in: | Frontiers in pharmacology 2022-06, Vol.13, p.892914-892914 |
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Sprache: | eng |
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Zusammenfassung: | 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,
1
H nuclear magnetic resonance and
13
C NMR spectral analysis. Subsequently,
in vitro
anticancer studies revealed that Compound 4b showed maximum cytotoxicity with IC
50
values of 1.539 μM/ml and 1.732 μM/ml against A549 and K562 cell lines respectively. This, however, is lower in comparison with standard Paclitaxel (IC
50
values of 0.3 μM/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. |
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ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2022.892914 |