Synthesis and topoisomerase I inhibitory properties of luotonin A analogues
[Display omitted] 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]q...
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Published in | Bioorganic & medicinal chemistry Vol. 12; no. 23; pp. 6287 - 6299 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.12.2004
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | [Display omitted]
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. |
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ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2004.08.052 |