Background/aim: 4H-1-Benzopyran-4-one (chromone), present in various flavonoids as a backbone structure, has been used for the synthesis of anticancer drugs. The study aimed at investigating the cytotoxicity of eight 2-arylazolylchromones and twelve 2-triazolylchromones against four human oral squamous cell carcinoma (OSCC) cell lines and three human normal mesenchymal oral cells, and then performed a quantitative structure-activity relationship (QSAR) analysis.
Materials and methods: Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The distribution of cells to various phases of cell cycle was determined by cell cycle analysis. A total of 3,218 physicochemical, structural and quantum chemical features were calculated for QSAR analysis from the most stabilized structure optimized using CORINA.
Results: 2-[4-(4-fluorophenyl)-1H-imidazol-1-yl]-4H-1-benzopyran-4-one [6] had the highest tumor-specificity (TS), comparable with that of 5-flurouracil (5-FU) and doxorubicin, inducing cytostatic growth inhibition, accumulation of G2+M phase cells with no cells in the G1 phase. All eight 2-triazolylchromones showed much lower tumor-specificity, confirming our previous finding. Tumor-specificity was also correlated with 3D shape, topological shape, size, ionization potential, and the presence of more than two aromatic rings in the molecule and imidazole ring in the nitrogen-containing heterocyclic ring.
Conclusion: [6] can be a lead compound for designing anticancer drugs.
Keywords: 2-Arylazolylchromones; 2-triazolylchromones; QSAR analysis; cell cycle analysis; cytotoxicity; molecular shape; tumor-selectivity.
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