Alkyl Esters of Camptothecin and 9-Nitrocamptothecin: Synthesis, in Vitro Pharmacokinetics, Toxicity, and Antitumor Activity
| Autor: | John S. Stehlin, Nick Harris, Dana Vardeman, Beppino C. Giovanella, Zhisong Cao, Anthony J. Kozielski |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Alkylation
Acylation Carboxylic acid Transplantation Heterologous Mice Nude Antineoplastic Agents Breast Neoplasms Pharmacology Mice Structure-Activity Relationship Nitrocamptothecin In vivo Drug Discovery medicine Animals Humans chemistry.chemical_classification Molecular Structure Transplantation chemistry Toxicity Molecular Medicine Camptothecin Female Lactone medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 41:31-37 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm9607562 |
| Popis: | Eleven camptothecin esters, 6a-e and 7a-f, were prepared by straightforward acylation of camptothecins with the corresponding acylating reagents such as organic anhydrides and carboxylic acid chlorides. The in vitro pharmacokinetic determination of lactone levels of esters 6a and 7b showed that the biological life span of their lactone forms in human and mouse plasma significantly increased when compared with their mother compounds, camptothecin (3) and 9-nitrocamptothecin (4). The differences of lactone levels between human plasma and mouse plasma for 6a and 7b were much smaller than what was observed for their mother compounds. The in vivo antitumor activity and toxicity studies demonstrated that some of these esters were very active against human tumor xenografts in nude mice and had an exceptional lack of toxicity in nude mice, even at enormous doses. |
| Databáze: | OpenAIRE |
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