Abstract
Luotonin A, a naturally occurring pyrroloquinazolinoquinoline alkaloid, has been previously demonstrated to be a topoisomerase I poison. A number of luotonin A derivatives have now been prepared through the condensation of anthranilic acid derivatives and 1,2-dihydropyrrolo[3,4-b]quinoline-3-one in the presence of phosphorus oxychloride. When dichloromethane was used as solvent the reaction proceeded to a single product. In contrast when the reaction was carried out in tetrahydrofuran or in phosphorus oxychloride, an additional isomeric product was obtained. The luotonin A analogues were evaluated for their ability to effect stabilization of the covalent binary complex formed between human topoisomerase I and DNA, and for cytotoxicity toward a yeast strain expressing the human topoisomerase I.
Original language | English (US) |
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Pages (from-to) | 6287-6299 |
Number of pages | 13 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 12 |
Issue number | 23 |
DOIs | |
State | Published - Dec 1 2004 |
Externally published | Yes |
Keywords
- Camptothecin
- Luotonin A
- Structure-activity relationships
- Topoisomerase I-DNA inhibition
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry