Potential Antimalarial Lead Structures from Fungi of Marine Origin

Abstract

Antiplasmodial and cytotoxicity testing of five highly oxygenated natural products (6R,12R,14R-colletoketol, 6R,11R,12R,14R-colletoketodiol, dihydrobotrydial, pycnidione, and 3R,4S-hydroxymellein), all derived from fungi of marine origin, showed one of them, pycnidione, to have activities against three different strains of Plasmodium falciparum in the sub-micromolar (μM) range. Although the mean selectivity index of 1 for the observed antiplasmodial activity of 4 is low, pycnidione’s usefulness as a potential lead structure should not be ignored.

References

• 1 Angerhofer C K, Pezzuto J, König G M, Wright A D, Sticher O. Antimalarial sesquiterpenes from the marine sponge Acanthella klethra .  J Nat Prod. 1992;  55 1787-9
• 2 König G M, Wright A D, Angerhofer C K. Antimalarial diterpene isonitriles, isothiocyanates and isocyanates from the tropical marine sponge Cymbastela hooperi n.sp.  J Org Chem. 1996;  61 3259-67
• 3 Wright A D, König G M, Angerhofer C K, Greenidge P, Linden A, Desqueyroux-Faundéz R. Antimalarial activity: The search for marine derived natural products which demonstrate selective antimalarial activity.  J Nat Prod. 1996;  59 710-6
• 4 Wright A D, Wang H, Gurrath M, König G M, Kocak G, Neumann G, Loria P, Foley M, Tilley L. Inhibition of heme (FP) detoxification processes underlies the antimalarial activity of terpene isonitrile compounds from marine sponges.  J Med Chem. 2001;  44 873-85
• 5 Ang K HK, Holmes M J, Higa T, Hamann M T, Kara U AK. In vivo antimalarial activity of the beta-carboline alkaloid manzamine A.  Antimicrob Agents Chemother. 2000;  44 1645-9
• 6 D’Ambrosio M, Guerriero A, Deharo E, Debitus C, Munoz V, Pietra F. New types of potentially antimalarial agents: epoxy-substituted norditerpene and norsesterpenes from the marine sponge Diacarnus levii .  Helv Chim Acta. 1998;  81 1285-92
• 7 El Sayed K A, Dunbar D C, Goins D K, Cordova C R, Perry T L, Wesson K J, Sanders S C, Janus S A, Hamann M T. The marine environment: a resource for prototype antimalarial agents.  J Nat Tox. 1996;  5 261-85
• 8 Gautret P, Le Pepe P, Biard J, Menard D, Verbist J, Marjolet M. The effects of bitramides on rodent malaria.  Acta Parasitol. 1998;  43 50-3
• 9 Miyaoka H, Shimura M, Kimura H, Yamada H. Antimalarial activity of kalihinol A and new relative diterpenoids from the Okinawan sponge, Acanthella sp.  Tetrahedron. 1998;  54 13 467-74
• 10 Osterhage C, Kaminsky R, König G M, Wright A D. Ascosalipyrrolidinone A, an antimicrobial alkaloid, from the obligate marine fungus Ascochyta salicorniae .  J Org Chem. 2000;  65 6412-7
• 11 Höller U, König G M, Wright A D. A new tyrosine kinase inhibitor from a marine isolate of Ulocladium botrytis and new metabolites from the marine fungus Asteromyces cruciatus and Varicosporina ramulosa . Eur J Org Chem 1999: 2949-55
• 12 Höller U. Isolation, biological activity and secondary metabolite investigations of marine derived fungi and selected host sponges. PhD dissertation, University of Braunschweig Braunschweig, Germany; 1999
• 13 Höller U, König G M, Wright A D. Three new metabolites from marine derived fungi of the genera Coniothyrium and Microsphaeropsis .  J Nat Prod. 1999;  62 114-8
• 14 Desjardins R E, Canfield C J, Haynes J D, Chulay J D. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.  Antimicrob Agents Chemother. 1979;  16 710-8