DNA Topoisomerase I Inhibitor, Ergosterol Peroxide from Penicillium oxalicum

Abstract

Recently, we found that the MeOH extract of Penicillium oxalicum showed inhibitory activity towards DNA topoisomerase I. Subsequently, ergosterol peroxide, ergosterol, palmitoleic acid, and linoleic acid were isolated from the cultured mycelia of P. oxalicum. The structural determinations were based on physical and spectral analyses. Biological evaluation revealed that ergosterol peroxide inhibited the relaxation of supercoiled DNA (pBR322) induced by DNA topoisomerase I, and also showed marginal, selective cytotoxic activity against human colon tumor cells [COLO-205 (ED₅₀) = 8.56 μg/mL].

References

• 1 Wang J C. DNA topoisomerases.  Annual Review of Biochemistry. 1996;  65 635-92
• 2 Heck M M, Hittelman W N, Eamshaw W C. Differential expression of DNA topoisomerases I and II during the eukaryotic cell cycle.  Proceedings of National Academy of Science of the United States of America. 1988;  85 1086-90
• 3 van der Zee A G, Hollema H, de Jong S, Boonstra H, Gouw A, Willemse P H, Zijlstra J G, De Vries E G. P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy.  Cancer Research. 1991;  51 5915-20
• 4 Verwij J. Topoisomerase I inhibitors and other new cytotoxic drugs.  European Journal of Cancer. 1995;  31A 828-30
• 5 Valenti M, Nieves-Neira W, Kohlhagen G, Kohn K W, Wall M E, Wani M C, Pommier Y. Novel 7-alkylmethylenedioxy-camptothecinderivatives exhibit increased cytotoxicity and induce persistent cleavable complexes both with purified mammalian topoisomerase I and in human colon carcinoma SW620 cells.  Molecular Pharmacology. 1997;  52 82-7
• 6 Takaishi Y, Uda M, Ohashi T, Nakano K, Murakami K, Tomimatsu T. Glycosides of ergosterol derivatives from Hericum erinacens .  Phytochemistry . 1991;  30 4117-20
• 7 Takaishi Y, Adachi R, Murakami T, Ohashi T, Nakano K, Tomimatsu T. A polyoxygenated steroid from Lasiosphaera nipponica .  Phytochemistry. 1992;  31 243-6
• 8 Rubinstein I, Goad L J, Clague A DH, Mulheirn L J. The 220 MHz NMR spectra of phytosterols.  Pytochemistry. 1976;  15 195-200
• 9 Leslie Gunatilaka A A, Gopichand Y. Schmitz FJ, Djerassi C. Minor and trace sterols in marine invertebrates. 26. Isolation and structure elucidation of nine new 5 α ,8 β -epidioxy sterols from four marine organisms.  Journal of Organic Chemistry. 1981;  46 3860-6
• 10 Pouchert C J, Behnke J. The Aldrich Library of 13C and 1H FT NMR Spectra, 1st edn. Milwaukee WI; Aldrich Chemical Co 1993 Vol. 1: pp 782-and 785
• 11 Kahlos K, Kangas L. Hiltunen R. Ergosterol peroxide, an active compound from Inonotus radiatus .  Planta Med. 1989;  55 389-90
• 12 Narbe G, Lindequist U, Teuscher E, Franke P. Vainiotalo P, Basner R. The chemistry of immunosuppressive acting fractions of Meripilus giganteus (Pers ex.Fr.) Karst., the giant spore.  Pharmazie. 1991;  46 738-40
• 13 Yasukawa K, Akihisa T, Kanno H, Kaminaga T, Izumida M, Sakoh T, Tamura T, Takido M. Inhibitory effects of sterols isolated from Chlorella vulgaris on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and tumor promotion in mouse skin. Biol.  Pharm Bull. 1996;  19 573-6
• 14 Kuo Y H, Li S Y, Shen Y C, Huang H C, Hsu Y W, Tseng R J, Ou J C, Chen C F. Sesquiterpene polyol esters and triterpenes from Celastrus punctatus .  Chinese Pharmaceutical Journal. 2001;  53 257-68
• 15 Sutapa R, Banasri H, Bidyottam M, Aditi D, Hemanta K M. Diospyrin, a bisnaphthoquinone: a novel inhibitor of type I DNA topoisomerase of Leishmania donovani .  Molecular Pharmacology. 1998;  54 994-9