Aims: This study aims are the synthesis of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1-
methylquinolin-2(1H)-ones and estimation their anticancer activities on HepG2 and KB cancer lines.
Background: Many derivatives of quinoline-2-on have been interested to synthesize and evaluate
their biological properties by organic chemists due to their various biological effects, including antibacterial,
antioxidant, anti-inflammatory, anticancer activities. Quinoline-pyrimidine hybrid compounds
exhibited various biological activities, such as antituberculosis, antibacterial, anticancer, antifungal,
etc. The connection of 4-hydroxyquinoline-2-one with 2-amino-pyrimidine could initiate the
Objective: α,β-Unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one were prepared.
Novel 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines have been synthesized
by reaction of these corresponding α,β-unsaturated ketones with guanidine hydrochloride. Human
hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines were used for screening
Methods: 3-Acetyl-4-hydroxy-N-methylquinolin-2-one was prepared from N-methylaniline and diethyl
malonate. Reaction of (un)substituted benzaldehydes with this 4-hydroxyquinoline-2-one produced
corresponding substituted α,β-unsaturated ketones in the presence of piperidine as catalyst. 2-
Amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines have been synthesized from
these α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding
α,β-unsaturated ketones with guanidine hydrochloride. All obtained pyrimidines were
screened for anticancer activity using MTT bio-assay method.
Results: Seven substituted (E)-4-hydroxy-3-(3-(aryl)acryloyl)-1-methylquinolin-2(1H)-ones were
prepared and converted to corresponding substituted 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-
2′-on-3′-yl)pyrimidines with yields of 58−74%. All the synthesized pyrimidines were screened for
their in vitro anticancer activity against human hepatocellular carcinoma HepG2 and squamous cell
carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC50 values
equal to 1.32 and 1.33 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f
possessed the drug-likeness behavior. Cross-docking results indicated that residues GLN778(A),
DT8(C), DT9(D), DA12(F), and DG13(F) in the binding pocket as potential ligand binding hot-spot
residues for compounds 6b, 6e, and 6f.
Conclusion: New substituted 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines
were obtained and displayed significant inhibition against human hepatocellular carcinoma HepG2
and squamous cell carcinoma KB cancer lines.