Synthesis of Some 1,2,3-triazole-bridged glycosides with benzoquniline-3-carbonitriles via click chemistry for anticancer, and docking evaluation

• Published in: Journal of molecular structure 2025-02, Vol.1321, p.139681, Article 139681
• Main Authors: El Malah, Tamer, El-Bayaa, Mohamed N., Abdelrahman, Mohamad Taha, Awad, Hanem M., Soliman, Hanan A.
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazoles; Benzoquniline-3-carbonitriles; Click chemistry Cytotoxic activity; Docking; Glycosides
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139681

•A novel series of 1,2,3-triazole-bridged glycosides with benzoquniline-3-carbonitriles was synthesized via click chemistry.•Spectroscopic data and elemental analysis confirmed the structure of the new compounds.•The newly synthesized compounds' cytotoxicity and in vitro anticancer activities were assessed against selected human cancerous cell lines.•The molecular docking results were compatible with the anticancer results. Novel benzoquniline-3-carbonitriles substituted 1,2,3-triazole glycosides were synthesized by using Cu(I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) known as Click reaction. The reaction of 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl and/or 2,3,4-tri-O-acetyl-β-d-xylopyranosyl azides 1,2 with the acetylenic arylbenzoqunioline-3-carbonitriles 3–6 afforded the corresponding 1,2,3-triazole acetylated N-glycoside products 7–11, which deacetylated using a saturated ammonia/methanol solution to produce the derived 1,2,3-triazole-N-glycosides 12–16, respectively. All the synthesized compounds have been characterized by IR, NMR (1H and 13C) spectroscopic techniques, mass spectra and elemental analyses. The desired products were examined against three tumor cells [the hepatocellular carcinoma (HepG2), breast (MCF-7), human colon (HCT-116), cancer cell lines] and one human healthy cell line (BJ-1) utilizing the LDH assay. In comparison to doxorubicin, most of the desired compounds can be considered as good anticancer candidate drugs for the liver, colon, and breast since their cytotoxic activity on each cancer type is greater than their cytotoxic activity on the normal cells. The molecular docking results were compatible with the anticancer results.