Aldophosphamide-thiazolidine (NSC-613060) an oxazaphosphorine cytostatic that crosses the blood brain barrier
| Autor: | G. Voelcker |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Cyclophosphamide medicine.medical_treatment Intraperitoneal injection Thiazolidine Apoptosis Pharmacology Blood–brain barrier 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Tumor Cells Cultured Animals Pharmacology (medical) Tissue Distribution Chronic toxicity Active metabolite Cell Proliferation Leukemia Experimental Chemistry Aldophosphamide Cytostatic Agents 030104 developmental biology medicine.anatomical_structure Oncology Blood-Brain Barrier 030220 oncology & carcinogenesis Nitrogen Mustard Compounds Thiazolidines Female Cysteine medicine.drug |
| Zdroj: | Anti-cancer drugs. 32(1) |
| ISSN: | 1473-5741 |
| Popis: | The pharmacologically active metabolite of cyclophosphamide is aldophosphamide. With cysteine, aldophosphamide forms stable aldophosphamide-thiazolidine which under physiological pH and temperature conditions hydrolyzes to aldophosphamide and cysteine. Aldophosphamide-thiazolidine was synthesized and tested for its ability as a cytostatic. The LD50 after a single intraperitoneal injection in mice was determined to be 2162 mg/kg, but after intravenous bolus administration of 500 mg/kg or in chronic toxicity tests with daily intraperitoneal injections, neurological side effects were observed. Antitumor activity was determined in therapy experiments in CD2F1 mice bearing subcutaneously transplanted P388 mouse leukemia cells. Administration of 100 mg/kg (less than 5% LD50) days 1-5 after tumor transplantation yielded an ILS of 100%. Organ distribution studies showed that aldophosphamide-thiazolidine is evenly distributed in all tissues examined, including brain tissue. The possibilities to increase the antitumor activity of aldophosphamide-thiazolidine by modulating the alkylating function are discussed. |
| Databáze: | OpenAIRE |
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