title: Antiparasitic activity of marine pyridoacridone alkaloids related to the ascididemins.
abstract: A series of pyridoacridone alkaloids, including the marine alkaloid ascididemin were tested in vitro for antiparasitic activity against P. falciparum (K1, NF54), L. donovani, T. cruzi, T. b. rhodesiense and two mammalian cell lines (L6, RAW 264.7). Most compounds showed high antiplasmodial activity, moderate antileishmanial activity against both extra- and intracellular forms, and significant trypanocidal effects against T. cruzi and T. b. brucei. However, when tested against mammalian cell lines, most of the compounds were also toxic for macrophage-like RAW 264.7 cells and skeletal muscle myoblast L6 cells. Correlations between molecular structures and antiparasitic activity are discussed in detail. Specific compounds are illustrated with emphasis on their potential as new antiparasitic drug leads.
authors.affiliation: Department of Chemistry, University of Auckland, Auckland, New Zealand.
authors.forename: Brent R
authors.initials: BR
authors.lastname: Copp
authors.forename: Oliver
authors.initials: O
authors.lastname: Kayser
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Albrecht F
authors.initials: AF
authors.lastname: Kiderlen
mesh_terms: D000166:Acridines / Q000737:chemistry; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line / Q000187:drug effects; D007893:Leishmania donovani / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D018482:Muscle, Skeletal / Q000187:drug effects; D032446:Myoblasts / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D010618:Phenanthrolines / Q000737:chemistry; D008517:Phytotherapy; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines; D051381:Rats; D013329:Structure-Activity Relationship; D014345:Trypanosoma / Q000187:drug effects*; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects; D014561:Urochordata
chemical_list: D000166:Acridines; D000470:Alkaloids; D000981:Antiprotozoal Agents; D010618:Phenanthrolines; D011804:Quinolines; C475900:pyridoacridine; C412046:ascididemin