Effect of modification of betulinic acid at the C3-carbon atom of homolupane triterpenoids on the antiproliferative activity in vitro

0562286 - ÚEB 2023 RIV GB eng J - Journal Article
Rárová, L. - Pakulski, Z. - Strnad, Miroslav - Kvasnicová, M. - Štenclová, T. - Cmoch, P.
Effect of modification of betulinic acid at the C3-carbon atom of homolupane triterpenoids on the antiproliferative activity in vitro.
Journal of Steroid Biochemistry and Molecular Biology. Roč. 224, NOV (2022), č. článku 106161. ISSN 0960-0760
R&D Projects: GA ČR(CZ) GA20-25308S
Institutional support: RVO:61389030
Keywords : Antiproliferative activity * Apoptosis * Cancer cells * Fibroblasts * Lupanes * Reformatsky reaction
OECD category: Medicinal chemistry
Impact factor: 4.1, year: 2022
Method of publishing: Open access
https://doi.org/10.1016/j.jsbmb.2022.106161

In search of new cytotoxic derivatives based on the lupane scaffold, methyl betulonate and methyl 20,29-dihydrobetulonate were conjugated with Reformatsky reagents to provide homolupanes extended at the C3-carbon atom. Further transformations of the functional groups afforded a series of derivatives with 2-hydroxyethyl and allyl alcohol moieties. Their varying antiproliferative activity in vitro was then investigated in four cancer cell lines and in normal human BJ fibroblasts. In cervical carcinoma HeLa cells, derivatives 5, 6 and 17 were the most promising with lower micromolar IC50s and no toxicity to fibroblasts, thus showing a high therapeutic index. In addition, induction of apoptosis was found in HeLa cells after 24 h treatment with compounds 5, 6, 13 and 29. This newly synthesized series is more interesting than the published lupane and homolupane triterpenes and saponins, due to their nontoxicity towards healthy human cells and stronger cytotoxicity to various cancer cell lines. This approach increases their potential as anticancer agents.
Permanent Link: https://hdl.handle.net/11104/0334634