Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065
| Autor: | William C. Krueger, I. Gebhard, M. D. Prairie, Martha A. Warpehoski, Wicnienski Nancy Anne, Kelly Robert C, J. P. McGovren, Wendell Wierenga, L. H. Li |
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| Rok vydání: | 1988 |
| Předmět: |
Drug
Indoles Chemical Phenomena Stereochemistry media_common.quotation_subject Alkylation Leucomycins Hydrophobic effect Duocarmycins Mice chemistry.chemical_compound Drug Discovery Animals Potency Leukemia L1210 media_common Antibiotics Antineoplastic Chemistry Physical Leukemia P388 Circular Dichroism Biological activity DNA Nuclear magnetic resonance spectroscopy Solubility chemistry Adozelesin Mice Inbred DBA Molecular Medicine Female |
| Zdroj: | Journal of Medicinal Chemistry. 31:590-603 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00398a017 |
| Popis: | The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effective than 1 against murine tumors. In particular, compound 27 exhibits high activity and potency. Structure-activity analysis supports a molecular mechanism for biological action involving hydrophobic interaction of the drug with DNA and acid-catalyzed alkylation of DNA. |
| Databáze: | OpenAIRE |
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