Synthesis and cytotoxic activity of 1,2,3-triazoles derived from 2,3-seco-dihydrobetulin via a click chemistry approach

Abstract
In search of new cytotoxic derivatives based on the lupane scaffold, the seco-lupane azides were coupled with a number of alkynes under the 1,3-dipolar cycloaddition (CuAAC) conditions to afford 1,2,3-triazoles. Phenylalkynes having different substituents at the para position were used as starting materials. Similarly, coupling of the seco-lupane thiocyanate with sodium azide gave 5-thiotetrazole. The cytotoxicity of thir- teen derivatives were investigated, as well as the effect of substituents in the phenyl ring on the activity of 1,2,3-triazoles. Limited activity was observed for some of these products. Most of the studied com- pounds were inactive in cancer cell lines and healthy fibroblasts. Triazole 46 exhibited cytotoxic activity against CEM and MCF-7 cancer cell lines, however, it was also toxic to normal human BJ fibroblasts. Two other derivatives – triazole 45 and tetrazole 49 – exhibited low cytotoxicity. Compound 49 showed good selectivity towards tumor cell lines compared to normal fibroblasts. This compound did not affect the growth of normal human fibroblasts and therefore has a wide therapeutic window.
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Kuczynska, Kinga & Bonczak, Bartlomiej & Rárová, Lucie & Kvasnicová, Marie & Strnad, Miroslav & Pakulski, Zbigniew & Cmoch, Piotr & Fialkowski, Marcin. (2022). Synthesis and cytotoxic activity of 1,2,3-triazoles derived from 2,3-seco-dihydrobetulin via a click chemistry approach. Journal of Molecular Structure. 1250. 131751. https://doi.org/10.1016/j.molstruc.2021.131751
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