Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; 3-AP): an inhibitor of ribonucleotide reductase with antineoplastic activity
| Autor: | Ann H. Cory, Joseph G. Cory, M.‐C. Liu, Alan C. Sartorelli, Rick Avery Finch |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Thiosemicarbazones
Cancer Research Pyridines Guanine Iron Drug Resistance Antineoplastic Agents In Vitro Techniques Pharmacology Mice chemistry.chemical_compound Deoxyribonucleotide Ribonucleotide Reductases Tumor Cells Cultured Genetics Animals Hydroxyurea Enzyme Inhibitors Leukemia L1210 Molecular Biology chemistry.chemical_classification Mice Inbred C3H Chemistry 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone DNA Neoplasm Ribonucleoside In vitro Enzyme Ribonucleotide reductase Mice Inbred DBA Molecular Medicine Female Cell Division Cytosine |
| Zdroj: | Advances in Enzyme Regulation. 39:3-12 |
| ISSN: | 0065-2571 |
| Popis: | The enzyme RR catalyzes the conversion of ribonucleoside diphosphates to their deoxyribonucleotide counterparts. RR is critical for the generation of the cytosine, adenine, and guanine deoxyribonucleotide 5'-triphosphate building blocks of DNA, which are present in cells as exceedingly small intracellular pools. Therefore, interference with the function of RR might well result in an agent with significant antineoplastic activity, particularly against rapidly proliferating tumor cells. HUr is the only inhibitor of RR in clinical usage; this agent, however, is a relatively poor inhibitor of the enzyme and has a short serum half-life. Consequently, HUr is a relatively weak anticancer agent. In an effort to develop a more potent inhibitor of RR with utility as an anticancer agent, we have synthesized 3-AP and demonstrated (a) potent inhibition of L1210 leukemia cells in vitro, (b) curative capacity for mice bearing the L1210 leukemia, (c) marked inhibition of RR, and (d) sensitivity of HUr-resistant cells to 3-AP. These findings collectively demonstrate the clinical potential of 3-AP as an antineoplastic agent. |
| Databáze: | OpenAIRE |
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