Picolyl amides of betulinic acid as antitumor agents causing tumor cell apoptosis

0488676 - ÚEB 2019 RIV FR eng J - Journal Article
Bildziukevich, Uladzimir - Rárová, L. - Šaman, David - Wimmer, Zdeněk
Picolyl amides of betulinic acid as antitumor agents causing tumor cell apoptosis.
European Journal of Medicinal Chemistry. Roč. 145, FEB 10 (2018), s. 41-50. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA MPO(CZ) FV10599
Institutional support: RVO:61389030 ; RVO:61388963
Keywords : Amide * Betulinic acid * Cytotoxicity * Picolyl amine * Therapeutic index
OECD category: Organic chemistry
Impact factor: 4.833, year: 2018

A series of picolyl amides of betulinic acid (3a–3c and 6a–6c) was prepared and subjected to the cytotoxicity screening tests. Structure-activity relationships studies resulted in finding differences in biological activity in dependence on o-, m- and p-substitution of the pyridine ring in the target amides, when cytotoxicity data of 3a–3c and 6a–6c were obtained and compared. The amides 3b and 3a displayed cytotoxicity (given in the IC 50 values) in G-361 (0.5 ± 0.1 μM and 2.4 ± 0.0 μM, respectively), MCF7 (1.4 ± 0.1 μM and 2.2 ± 0.2 μM, respectively), HeLa (2.4 ± 0.4 μM and 2.3 ± 0.5 μM, respectively) and CEM (6.5 ± 1.5 μM and 6.9 ± 0.4 μM, respectively) tumor cell lines, and showed weak effect in the normal human fibroblasts (BJ). Selectivity against all tested cancer cells was determined and compared to normal cells with therapeutic index (TI) between 7 and 100 for compounds 3a and 3b. The therapeutic index (TI = 100) was calculated for human malignant melanoma cell line (G-361) versus normal human fibroblasts (BJ). The cytotoxicity of other target amides (3c and 6a–6c) revealed lower effects than 3a and 3b in the tested cancer cell lines.
Permanent Link: http://hdl.handle.net/11104/0283229