Picolyl amides of betulinic acid as antitumor agents causing tumor cell apoptosis
Language English Country France Media print-electronic
Document type Journal Article
PubMed
29316537
DOI
10.1016/j.ejmech.2017.12.096
PII: S0223-5234(17)31126-1
Knihovny.cz E-resources
- Keywords
- Amide, Betulinic acid, Cytotoxicity, Picolyl amine, Therapeutic index,
- MeSH
- Amides chemical synthesis chemistry pharmacology MeSH
- Apoptosis drug effects MeSH
- Cell Line MeSH
- Betulinic Acid MeSH
- Humans MeSH
- Molecular Structure MeSH
- Pentacyclic Triterpenes MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Triterpenes chemical synthesis chemistry pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Amides MeSH
- Betulinic Acid MeSH
- Pentacyclic Triterpenes MeSH
- Antineoplastic Agents MeSH
- Triterpenes MeSH
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 IC50 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.
References provided by Crossref.org
Cytotoxicity and Nanoassembly Characteristics of Aromatic Amides of Oleanolic Acid and Ursolic Acid
Biocatalysis in the Chemistry of Lupane Triterpenoids
Synthesis and Pharmacological Effects of Diosgenin-Betulinic Acid Conjugates
