Ellipticine is a known intercalator, capable of entering a DNA strand between base pairs. In its intercalated state, ellipticine binds strongly[9] and lies parallel to the base pairs,[10] increasing the superhelical density of the DNA.[11] Intercalated ellipticine binds directly to topoisomerase II, an enzyme involved in DNA replication,[12] inhibiting the enzyme and resulting in powerful antitumour activity.[10] In clinical trials, ellipticine derivatives have been observed to induce remission of tumour growth, but are not used for medical purposes due to their high toxicity; side effects include nausea and vomiting, hypertension, cramp, pronounced fatigue, mouth dryness, and mycosis of the tongue and oesophagus.[13]
Further DNA damage results from the formation of covalent DNA adducts following enzymatic activation of ellipticine by with cytochromesP450 and peroxidases, meaning that ellipticine is classified as a prodrug.[14]
References
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Miller, R B; Dugar, S (1989). "A regiospecific total synthesis of ellipticine via nitrene insertion". Tetrahedron Letters. 30 (3): 297–300. doi:10.1016/S0040-4039(00)95184-0. ISSN0040-4039.
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Sbai, M; Ait Lyazidi, S; Lerner, D A; del Castillo, B; Martin, M A (1996). "Use of micellar media for the fluorimetric determination of ellipticine in aqueous solutions". Journal of Pharmaceutical and Biomedical Analysis. 14 (8): 959–965. doi:10.1016/S0731-7085(96)01759-1. ISSN0731-7085. PMID8818001.
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Goodwin, S; Smith, A F; Horning, E C (1959). "Alkaloids of Ochrosia elliptica Labill". Journal of the American Chemical Society. 81 (8): 1903–1908. doi:10.1021/ja01517a031.
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Paoletti, C; Le Pecq, J B; Dat-Xuong, N; Juret, P; Garnier, H; Amiel, J L; Rouesse, J (1980). "Antitumor Activity, Pharmacology, and Toxicity of Ellipticines, Ellipticinium, and 9-Hydroxy Derivatives: Preliminary Clinical Trials of 2-Methyl-9-Hydroxy Ellipticinium (NSC 264-137)". Cancer Chemo- and Immunopharmacology. Recent Results in Cancer Research. Vol. 74. pp. 107–123. doi:10.1007/978-3-642-81488-4_15. ISBN978-3-642-81490-7. ISSN0080-0015. PMID7003658. {{cite book}}: |journal= ignored (help)
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Stiborová, M; Poljaková, J; Martínková, E; Ulrichová, J; Šimánek, V; Dvořák, Z; Frei, E (2012). "Ellipticine oxidation and DNA adduct formation in human hepatocytes is catalyzed by human cytochromes P450 and enhanced by cytochrome b5". Toxicology. 302 (2–3): 233–241. doi:10.1016/j.tox.2012.08.004. ISSN0300-483X. PMID22917556.