title: Synthesis and biological evaluation of new derivatives of emodin.
abstract: Drugs containing an anthraquinone moiety such as daunorubicin (Daunoblastin) and mitoxantrone (Onkotrone) constitute some of the most powerful cytostatics. They suppress tumor growth mainly by intercalation into DNA and inhibition of topoisomerase II, and are suspected to generate free radicals leading to DNA strand scission. We established a novel strategy for obtaining new highly functionalized derivatives of emodin (1,3,8-trihydroxy-6-methyl-anthraquinone). Using emodin, DIB, and an appropriate amine as starting materials, we obtained a wide range of emodin-related structures by one-pot synthesis. Several of these derivatives showed stronger cytotoxic and cytostatic activity than emodin. In particular, compound 6 was highly effective on the HepG2 tumor cell line, but did not show any cytotoxicity on normal hepatocytes. In addition to this favorable feature, compound 6 revealed interesting binding properties to a recombinant fragment of the multi-drug-resistance transporter, pgp, and reversed the multi-drug-resistance phenotype of H4-II-E cells, thus making this compound a promising potential anti-tumor drug.
authors.affiliation: Institut für Pharmazie, Fakultät für Biowissenschaften, Pharmazie und Psychologie, Universität Leipzig, Brüderstrasse 34, 04103 Leipzig, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Teich
authors.forename: Katja Scarlett
authors.initials: KS
authors.lastname: Daub
authors.forename: Vera
authors.initials: V
authors.lastname: Krügel
authors.forename: Ludwig
authors.initials: L
authors.lastname: Nissler
authors.forename: Rolf
authors.initials: R
authors.lastname: Gebhardt
authors.forename: Kurt
authors.initials: K
authors.lastname: Eger
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004642:Emodin / Q000138:chemical synthesis* / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051381:Rats
chemical_list: D004642:Emodin