Cagir Ali, Eisenhauer Brian M, Gao Rong, Thomas Shannon J, Hecht Sidney M
Department of Chemistry and Department of Biology, University of Virginia, Charlottesville, VA 22901, USA.
Bioorg Med Chem. 2004 Dec 1;12(23):6287-99. doi: 10.1016/j.bmc.2004.08.052.
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.
路托替尼A是一种天然存在的吡咯并喹唑啉喹啉生物碱，此前已被证明是一种拓扑异构酶I毒药。现在通过邻氨基苯甲酸衍生物与1,2-二氢吡咯并[3,4-b]喹啉-3-酮在三氯氧磷存在下缩合制备了多种路托替尼A衍生物。当使用二氯甲烷作为溶剂时，反应生成单一产物。相反，当反应在四氢呋喃或三氯氧磷中进行时，会得到一种额外的异构体产物。对路托替尼A类似物进行了评估，以考察它们对人拓扑异构酶I与DNA形成的共价二元复合物的稳定作用能力，以及对表达人拓扑异构酶I的酵母菌株的细胞毒性。
