Development of a d-allose-6-phosphate derivative with anti-proliferative activity against a human leukemia MOLT-4F cell line
| Autor: | Yasuhiro Kawanami, Ryo C. Yanagita, Yasunori Sugiyama, Kazune Takemoto, Katsuya Kobashi, Hironobu Ishiyama |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Molecular Conformation
Antineoplastic Agents 010402 general chemistry 01 natural sciences Biochemistry Analytical Chemistry chemistry.chemical_compound Structure-Activity Relationship Drug Development medicine Tumor Cells Cultured Monosaccharide Humans Cytotoxicity Cell Proliferation chemistry.chemical_classification Dose-Response Relationship Drug 010405 organic chemistry Organic Chemistry General Medicine Prodrug medicine.disease Molecular biology 0104 chemical sciences Leukemia chemistry Cell culture Allose Epimer Drug Screening Assays Antitumor TXNIP |
| Zdroj: | Carbohydrate research. 487 |
| ISSN: | 1873-426X |
| Popis: | d-Allose, a C-3 epimer of d-glucose, is a naturally occurring rare monosaccharide that shows anti-proliferative activity against several human cancer cell lines. However, d-allose requires a relatively high concentration for the activity to be observed. Thus, developing more potent derivatives is needed for application. In cells, d-allose is converted to d-allose-6-phosphate (A6P), which is responsible for the anti-proliferative activity of d-allose. In this study, we synthesized A6P derivative 1 with biodegradable protecting groups, which showed higher anti-proliferative activity than A6P against a MOLT-4F human leukemia cell line. Similarly protected derivative of d-glucose-6-phosphate (G6P) (2) and tetraacetyl-A6P (3) showed weaker and less activity compared with 1, respectively, suggesting that both A6P moiety and the protecting group on the phosphate group are responsible for the activity. In addition, significantly weaker induction of thioredoxin-interacting protein (TXNIP) expression by 1 compared with d-allose suggests that 1 exhibited cytotoxicity through the synergetic effect of inducing TXNIP expression and other mechanisms. |
| Databáze: | OpenAIRE |
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