Abstract
Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic acid, through concise 1,2,3-triazole synthesis via click chemistry approach at C-3position in ring A have been evaluated for their cytotoxic potentiation against nine human cancer cell lines. Most of the derivatives have shown higher cytotoxic profiles than the parent molecule. Two compounds i.e. 3{1N(2-cyanophenyl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (7) and 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (13) displayed impressive IC50 values (2.5 and 3.5 μM respectively) against leukemia cell line HL-60 (5-7-fold higher potency than betulinic acid). As evident from various biological end points, inhibition of cell migration and colony formation, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis, is demonstrated.
| Original language | English |
|---|---|
| Journal | European Journal of Medicinal Chemistry |
| Volume | 63 |
| Pages (from-to) | 782-92 |
| Number of pages | 11 |
| ISSN | 0223-5234 |
| DOIs | |
| Publication status | Published - May 2013 |
Keywords
- Apoptosis
- Cell Line, Tumor
- Cell Movement
- Cell Survival
- DNA Fragmentation
- Dose-Response Relationship, Drug
- Electrophoresis, Agar Gel
- HL-60 Cells
- Humans
- Inhibitory Concentration 50
- MCF-7 Cells
- Membrane Potential, Mitochondrial
- Models, Chemical
- Molecular Structure
- Structure-Activity Relationship
- Triazoles
- Triterpenes
- Journal Article
- Research Support, Non-U.S. Gov't
