Synthesis and biological activities of new furo[3,4-b]carbazoles: Potential topoisomerase II inhibitors

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• 作者：Youssef Hajbi ; Clé ; opatra Neagoie ; Bé ; renger Biannic ; Auré ; lie Chilloux ; Emeline Vedrenne ; Brigitte Baldeyrou ; Christian Bailly ; Jean-Yves Mé ; rour ; Sorin Rosca ; Sylvain Routier ; Amé ; lie Lansiaux
• 关键词：Carbazoles ; Synthesis ; Azatoxin ; Microwave ; Topoisomé ; rase II ; Inhibition cytotoxicity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：November 2010
• 年：2010
• 卷：45
• 期：11
• 页码：5428-5437
• 全文大小：476 K

文摘

New 1,5-Dihydro-4-(substituted phenyl)-3H-furo[3,4-b]carbazol-3-ones were synthesised via a key step Diels–Alder reaction under microwave irradiation. 3-Formylindole was successfully used in a 6-step synthesis to obtain those complex heterocycles. The Diels–Alder reaction generating the carbazole ring was optimised under thermal conditions or microwave irradiation. After cleavage of functional groups, DNA binding, topoisomerase inhibition and cytotoxic properties of the new-formed furocarbazoles were investigated. These carbazoles do not present a strong interaction with the DNA, and do not modify the relaxation of the DNA in the presence of topoisomerase I or II except for one promising compound. This compound is a potent topoisomerase II inhibitor, and its cellular activity is not moderated compared to etoposide. The synthesis of these molecules allowed the generalisation of the method using indole and 5-OBn indole and several benzaldehydes. The synthesis of these molecules produced chemical structures endowed with promising cytotoxic and topoisomerase II inhibition activities.