Issue in Honor of Prof. Otto Gottlieb ARKIVOC 2004 (vi) 89-94 ISSN 1424-6376 Page 89 © ARKAT USA, Inc Cytotoxicity of derivatives of oncocalyxone A from Auxemma oncocalyx Taub Cláudia Pessoa, 1 * Telma L.G. Lemos, 2 Otília D.L. Pessoa, 2 Manoel O. Moraes, 1 Denissa Vasconcellos, 1 Letícia V. Costa-Lotufo, 1 and Albert Leyva 3 1 Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Caixa Postal 3157, 60430-970, Fortaleza, CE, Brasil. 2 Departamento de Química Orgânica e Inorgânica Universidade Federal do Ceará, Caixa Postal 12200, 60021-940, Fortaleza, CE, Brasil 3 Department of Pharmacology, University of Missouri, Kansas City, 2411 Holmes, Kansas City, MO 64108 E-mail: cpessoa@ufc.br Dedicated to Professor Otto Richard Gottlieb on his 85 th birthday (received 24 Nov 04; accepted 30 July 04; published on the web 05 Aug 04) Abstract Oncocalyxone A (1) (rel-8α-hydroxy-5-hydroxymethyl-2-methoxy-8aβ-methyl-7,8,8a,9- tetrahydro-1,4-anthracenedione) is a 1,4-anthracenedione that has been shown to be cytotoxic to human tumor cells and to be DNA reactive. Three derivatives of 1 obtained by chlorination (6- chloro-oncocalyxone A, 2) and acetylation (11-O-acetyloncocalyxone A, 3; 8,11-O- diacetyloncocalyxone A, 4) were found to be less cytotoxic and less DNA reactive in human leukemia cells. These derivatives were less polar compounds with modifications that may have hindered binding of the compound to DNA. Keywords: Oncocalyxone A, cytotoxicity, anthracenedione, Auxemma oncocalyx, natural products Introduction In an earlier paper, we reported on the in vitro cytotoxicity of several compounds isolated from plants commonly used in Brazilian traditional medicine 1 . One of the most potent compounds was a 1,4-anthracenedione isolated from Auxemma oncocalyx (Boraginaceae) 2 , a common tree found only in Ceará state, Brazil 3 . The ethanol extract of the heartwood yields rel-8α-hydroxy-5- hydroxymethyl -2 –methoxy – 8aβ –methyl -7,8,8a,9 -tetrahydro-1,4-anthracenedi- one, given the common name oncocalyxone A (Figure 1). Cytotoxicity was demonstrated in vitro in a panel of human cancer cell lines with IC 50 values ranging 1-18 μg/mL. Oncocalyxone A was most toxic to CEM leukemia cells and caused DNA damage. However, its potency is still relatively