Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an antineoplastic agent that intercalates into DNA and alters topoisomerase II activity. Unfortunately, this compound displays a number of adverse properties. Therefore, to investigate new ellipticine-based compounds for their potential as topoisomerase II-targeted drugs, we synthesized two novel derivatives, N-methyl-5-demethyl ellipticine (ET-1) and 2-methyl-N-methyl-5-demethyl ellipticinium iodide (ET-2). As determined by DNA decatenation and cleavage assays, ET-1 and ET-2 act as catalytic inhibitors of human topoisomerase IIα and are both more potent than the parent compound. Neither compound impairs the ability of the type II enzyme to bind its DNA substrate. Finally, the potency of ET-1 and ET-2 as catalytic inhibitors of topoisomerase IIα appears to be related to their ability to intercalate into the double helix.
Key indicators: single-crystal X-ray study; T = 296 K; mean (C-C) = 0.002 Å; R factor = 0.049; wR factor = 0.133; data-to-parameter ratio = 15.1.In the title compound, C 17 H 17 NO 2 , the carbazole skeleton includes an ethoxycarbonyl group at the 3-position. The indole three-ring system is almost planar [maximum deviation = 0.065 (2) Å ], and the ethyl ester group is inclined to its mean plane by 15.48 (2) . In the crystal, there are -stacking interactions between parallel benzene rings and between parallel benzene and pyrrole rings of adjacent molecules [centroid-centroid distances = 3.9473 (8) and 3.7758 (8) Å , respectively]. Weak C-HÁ Á Á interactions are also present.
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In the title compound, C15H15NO, the carbazole skeleton includes a methanol group at the 3-position. The indole ring system is almost planar [maximum deviation = 0.045 (2) Å]. In the crystal, O—H⋯O hydrogen bonds link the molecules into zigzag chains along the b-axis direction. There are weak C—H⋯π interactions within the chains and linking neighbouring chains forming sheets lying parallel to (001).
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