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

0563377 - ÚEB 2023 RIV NL eng J - Článek v odborném periodiku
Kuczynska, K. - Bończak, B. - Rárová, L. - Kvasnicová, M. - Strnad, Miroslav - Pakulski, Z. - Cmoch, P. - Fiałkowski, M.
Synthesis and cytotoxic activity of 1,2,3-triazoles derived from 2,3-seco-dihydrobetulin via a click chemistry approach.
Journal of Molecular Structure. Roč. 1250, č. 1 (2022), č. článku 131751. ISSN 0022-2860. E-ISSN 1872-8014
Grant CEP: GA ČR(CZ) GA20-25308S
Institucionální podpora: RVO:61389030
Klíčová slova: 5-Thiotetrazole * Betulin * Click chemistry * Cytotoxicity * Lupane * sar * Triazole
Obor OECD: Medicinal chemistry
Impakt faktor: 3.8, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1016/j.molstruc.2021.131751

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 thirteen 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 compounds 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.
Trvalý link: https://hdl.handle.net/11104/0335358