New Synthetic Derivatives from Peroxisomicine A1 and their Biological Activity

Abstract

Peroxisomicine A1 (PA1) is a dimeric anthracenone obtained from plants of the genus Karwinskia. Toxicological studies have demonstrated a selective toxicity of peroxisomicine A1 on various human tumor cell lines in vitro. For this reason it has been considered as a possible antineoplastic agent. This article describes the chemical manipulation of this compound with the purpose of finding a possible relationship between the structure and biological activity. Derivatization procedures on the phenolic OH groups, carbonyl group and aromatic ring are presented. Six new compounds were obtained and purified by several chromatographic methods and the pure products were identified and characterized by UV, IR, MS, and 1 H and 13 C NMR. To evaluate the biological activity of the derivatives, the selective cytoxicity of the compounds on normal and neoplastic human liver cells lines and their effect on catalase activity were analyzed. Cytotoxicity of compounds 2 - 5 suggests that phenolic groups are necessary for the biological action reported for PA1. On the other hand, compound 6, substituted on the aromatic ring, did not show a significant difference in the selective cytotoxicity assay when compared to peroxisomicine A1.