Synthesis and Evaluation of New 1,2,3‐triazole Alkyl Derivatives and Their Salts Against Breast Cancer Cells

• Published in: ChemistrySelect (Weinheim) 2024-02, Vol.9 (6), p.n/a
• Main Authors: De Paula, Wenderson T., Glanzmann, Nicolas, Da Costa Nunes, Isabelle K., Bento, Larissa P., Marcelo Gualberto Pereira, Henrique, De Souza‐Fagundes, Elaine M., Da Silva, Adilson D.
• Format: Article
• Language: English
• Subjects: 1,2,3-triazoles; antitumor; mammary cells; organic salts; phenols
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202303321

Breast cancer is responsible for causing the death of women across various age groups worldwide. Alkylphosphocholines such as miltefosine are attractive for the chemical therapy of this neoplasm, but have disadvantages such as gastrointestinal problems, occasional hepatotoxicity and nephrotoxicity, and potential teratogenicity. In the present study, a series of 1‐alkyl‐1,2,3‐triazoles and organic salts were synthesized, as new non‐classical miltefosine bioisosteres, and biological studies were performed using human cells from the triple‐negative MDA‐MB‐231 breast cancer. The results showed that 1,2,3‐triazolic salts substituted with aliphatic chains of 16 carbons showed antitumor action, with half‐maximum inhibitory concentration values between 3.2 and 6.4 μM. Furthermore, clonogenic assays were conducted to predict the chemosensitivity of the most promising compounds, which supported the findings from the IC50 values, highlighting two main compounds with significant efficacy in reducing clonogenic survival compared to the control group. In conclusion, two 1,2,3‐triazolic salts exhibited promising antitumor effects and warrant further investigation for potential therapeutic use against the disease. Novel organic salts were obtained from alkyl‐1,2,3‐triazoles with different substituents in position 4. After characterization, the synthesized derivatives were assayed against breast cancer cells, providing low IC50 values, and submitted to a clonogenic survival assay, in which two of the compounds were efficient in reducing clonogenic survival.