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

Abstract

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.

Graphical Abstract

Keywords:

• Click chemistry
• 123-triazole
• azide-alkyne cycloaddition
• anticancer activity
• molecular docking

Acknowledgments

The authors would like to extend their sincere appreciation to the National Research Centre and Egyptian Atomic Energy Authority.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

T. El Malah Conducting experiments, execution, methodology, conceptualization, analysis of compounds, and writing the original draft. H. Farag: Conducting experiments, methodology, and editing. H.M. Awad: Conducting anticancer analyses, writing biological section, and editing. M.T. Abdelrahman: Conducting molecular docking, writing docking section, and editing. A.H. Shamroukh: Data curation, reviewing, and editing. All authors have participated in the editing, revision and agreed to the published version of the manuscript.