Castalagin and vescalagin purified from leaves of Syzygium samarangense (Blume) MerrillL.M. Perry: Dual inhibitory activity against PARP1 and DNA topoisomerase II
| Autor: | Megumi Kato, Maria Shimoji, Akikazu Sakudo, Ayumi Tamanaha, Ikuko Miyagi, Chie Norimoto, Yasuharu Tanaka, Yasuhiro Kamada, Risa Yamashiro, Hibiki Yakabu, Toshio Ichiba |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Syzygium Poly (ADP-Ribose) Polymerase-1 Inhibitory postsynaptic potential 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine PARP1 Cell Line Tumor Drug Discovery Humans Topoisomerase II Inhibitors Poly-ADP-Ribose Binding Proteins IC50 Polymerase Pharmacology biology Topoisomerase General Medicine biology.organism_classification Hydrolyzable Tannins Plant Leaves 030104 developmental biology DNA Topoisomerases Type II Biochemistry chemistry 030220 oncology & carcinogenesis biology.protein Epimer Castalagin |
| Zdroj: | Fitoterapia. 129 |
| ISSN: | 1873-6971 |
| Popis: | Inhibition of poly(ADP-ribose) polymerase 1 (PARP1) is one of the most promising strategies for cancer chemotherapy, and a number of inhibitors possessing nicotinamide-like structures are being developed. To discover new types of PARP1 inhibitors, we screened a large number of substances of plant origin and isolated two inhibitory substances from the leaves of Syzygium samarangense (Blume) Merrill & L.M. Perry. The inhibitory substances were identified as vescalagin and its epimer castalagin by analyses using nuclear magnetic resonance and mass spectrometry. The IC50 of purified vescalagin and castalagin for PARP1 inhibition were 2.67 and 0.86 μM, respectively. Unlike most of synthetic PARP1 inhibitors, castalagin showed a mixed type inhibition, of which Ki was 1.64 μM. When SH-SY5Y cells were treated with these ellagitannins at concentrations of less than 5 μM, cellular poly(ADP-ribosyl)ation was obviously attenuated. Castalagin and vescalagin also possessed inhibitory activity against DNA topoisomerase II, implying that they function as dual inhibitors in cells. |
| Databáze: | OpenAIRE |
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