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Synthesis and antitumor activity of tropolone derivatives. 6. Structure-activity relationships of antitumor-active tropolone and 8-hydroxyquinoline derivatives.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1987 Oct; Vol. 30 (10), pp. 1897-900. - Publication Year :
- 1987
-
Abstract
- The bis derivative 6 of 8-hydroxyquinoline, which, like tropolones, readily forms a chelate, was synthesized and found to have high potency (dose = 12.5 mg/kg, T/C % = 164) against leukemia P388 in mice approximately equivalent to that of the bistropolone 1b. 8-Hydroxyquinoline analogues with broad structural variation were synthesized and their structure-activity relationships followed the same pattern as in the tropolone series. In addition, the bistropolones 1a-e were tested for their ability to bind to tubulin and found to have no such property. The results of this study suggested that bistropolone and bis(8-hydroxyquinoline) derivatives must form a chelate with the metal necessary for the enzyme, such as ribonucleotide reductase, which catalyzes the DNA biosynthetic pathways.
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Colchicine metabolism
Leukemia P388 drug therapy
Mice
Structure-Activity Relationship
Tropolone chemical synthesis
Tropolone therapeutic use
Antineoplastic Agents chemical synthesis
Cycloheptanes
Hydroxyquinolines
Oxyquinoline
Tropolone analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 30
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 3116257
- Full Text :
- https://doi.org/10.1021/jm00393a035