Design and Click Synthesis of Novel 1-Substituted-4-(3,4-Dimethoxyphenyl)-1H-1,2,3-Triazole Hybrids for Anticancer Evaluation and Molecular Docking

In an attempt to improve the performance of biologically active anticancer agents, a novel series of 1-substituent-4-(3,4-dimethoxyphenyl)-1H-1,2,3-triazole hybrids 10-16 were designed and efficiently synthesized via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions of 4-ethynyl-1,2-dimethoxybenzene 1 with substituted-azides 2-8. The structure of the new clicked 1,2,3-triazole hybrids 10-16 was confirmed on the basis of their elemental analysis and spectral data. Moreover, the cytotoxicity and in vitro anticancer activities of the newly synthesized compounds were also assessed against four different human cancer cell lines: Colon cancer (HCT116), Hepatocellular carcinoma (Hep G2), Breast cancer (MCF-7), and Lung carcinoma (A549). Among all the tested compounds, compound 15 revealed a higher potency against HCT116 compared to the activity of the reference drug, doxorubicin. This makes it an interesting candidate for further biological evaluation. Finally, a good correlation was obtained between the observed cytotoxicity evaluation of compound 15 against HCT116, from one side, and the molecular descriptors from another side.