The Synthetic Pathways of a New 1,2,3-Triazole-Containing Sorafenib Analogue and Its Cytotoxicity towards Cancer Cell Lines
Keywords:
sorafenib analogue, 1,2,3-triazole, cytotoxicity towards cancer cell lines, multikinase inhibitor, click reactionAbstract
Sorafenib (1) is a targeted cancer drug, which was approved by the Food and Drug Administration of the United States (US FDA) for the treatment of advanced hepatocellular carcinoma, renal cell carcinoma and thyroid carcinoma. In addition, sorafenib shows ability to inhibit various cancer cell lines due to its multikinase-inhibitory activity. However, sorafenib exhibits several disadvantageous pharmacological properties resulting in many adverse effects. Hence, many researchers are interested in design and synthesis to overcome the problems, and to search for their anti-tumor activities. Herein, the triazole-containing sorafenib analogue 2 was successfully synthesized by two different pathways. In the former pathway, 1,2,3-triazole ring was constructed via click reaction followed by aryl urea formation, which was suitable for the synthesis of analogues 14 with various substituted aryl moieties. The latter pathway started with linking aryl with urea and then click reaction for the triazole ring generation which was suitable for the synthesis of analogue 2 and the serial preparation of the substituted benzyl analogues 15. The study of biological activities towards cancer cell lines using MTT assay revealed that analogue 2 were inactive against MOLT-3, A549 and HuCCA-1 with IC50 > 100 µM. However, the obtained evidences will be an important guideline for the syntheses of the aryl- and benzyl-substituted analogues 14 and 15, which can be potentially active towards various cancer cell lines including liver cancer cell lines.
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