Background: According to WHO, in 2017, about 90.5 million people suffered from
cancer and about 8.8 million deaths occurred due to disease. Although the chemotherapeutic
agents have decreased the mortality among the cancer patients but high toxicity and non-specific
targets are still major drawbacks.
Many researchers have identified linomide, a 4-hydroxy-2-quinolone derivative, as a lead molecule for
the development of anticancer agents. With this background, we thought of the following objective.
Objective: The objective of this research work involves the synthesis of a series of N-(2-(4-
hydroxy-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-oxoethyl)-N-alkyl substituted benzene
sulfonamides IVa-d (1-3) by replacing the anilide moiety at the third position of linomide with
sulfamoylacyl and also N-methyl by N-phenyl functionality. To perform in silico anticancer activity
by using Molegro Virtual Docker (MVD-2013, 6.0) software and in vitro anticancer activity
by MTT assay.
Methods: The starting material 4-hydroxy-1-phenylquinolin-2(1H)-one was treated with N-bromosuccinamide
to yield compound II. Condensation of compound II with primary amines resulted in
compounds IIIa-d, which, on coupling with substituted aromatic sulfonyl chlorides yield the title
compounds IVa-d (1-3).
Results: All the synthesized compounds were satisfactorily characterized by spectral data. The results
of docking revealed that the synthesized compounds exhibited well-conserved hydrogen
bonds with one or more amino acid residues in the active pocket of EGFRK tyrosine kinase domain
(PDB ID: 1m17). The MolDock Score of compound IVd-1 (-115.503) was the highest
amongst those tested. The in vitro anticancer activity results showed that compound IVc-1 (R= -
(CH2) 2-CH3 ; R′= -H) and IV d-1 (R= -CH2-C6H5; R′= -H) were found to be most potent against
K562 cell line with an IC50 of 0.451 μM/ml and 0.455 μM/ml respectively. Compound IVd-1 also
showed better potency against A549 cell line with IC50 value of 0.704 μM/ml.
Conclusion: The results of in silico and in vitro anticancer activity are in agreement with each other.
Compound IV d-1 was found to be most active of the series.