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

New 1,5-Dihydro-4-(substituted phenyl)-3 H-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...

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Veröffentlicht in:European journal of medicinal chemistry 2010-11, Vol.45 (11), p.5428-5437
Hauptverfasser: Hajbi, Youssef, Neagoie, Cléopatra, Biannic, Bérenger, Chilloux, Aurélie, Vedrenne, Emeline, Baldeyrou, Brigitte, Bailly, Christian, Mérour, Jean-Yves, Rosca, Sorin, Routier, Sylvain, Lansiaux, Amélie
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Sprache:eng
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Zusammenfassung:New 1,5-Dihydro-4-(substituted phenyl)-3 H-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. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2010.09.003