Design, synthesis, and biological evaluation of novel asiatic acid derivatives as potential anticancer agents
| Autor: | Diana Santos, Silvia Marin, Marta Cascante, Bruno M. F. Gonçalves, Jorge A. R. Salvador |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cisplatin biology Chemistry General Chemical Engineering General Chemistry Cell cycle Pharmacology biology.organism_classification Jurkat cells HeLa 03 medical and health sciences 030104 developmental biology Biochemistry Apoptosis ASIATIC ACID Cell culture Cancer cell medicine medicine.drug |
| Zdroj: | RSC Adv.. 6:39296-39309 |
| ISSN: | 2046-2069 |
| DOI: | 10.1039/c6ra04597a |
| Popis: | A series of new asiatic acid derivatives modified in the A-ring and at C-28 were synthesized and their antiproliferative activity was evaluated against HT-29 and HeLa cell lines. Most of the derivatives tested here exhibited improved antiproliferative activity compared with asiatic acid. Among them, the best compounds, 7 and 8, were further evaluated against additional cancer cell lines (MCF-7, Jurkat, and PC-3 cells) and a nontumoral cell line (BJ). The most active compound, 7, exhibited IC50 values ranging from 1.62 μM in HeLa cells to 9.93 μM in MCF-7 cells. Further studies revealed that compound 7 arrested the cell cycle at the G0/G1 phase and induced caspase-dependent apoptosis in HeLa cells. Furthermore, this compound showed selectivity toward cancer cells, and a synergistic effect was observed after simultaneous treatment of HeLa cells with compound 7 and cisplatin. Collectively, our results suggest that compound 7 may be useful for the development of new anticancer therapies; thus, additional preclinical studies are warranted. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|