title: In vitro study of anticancer acridines as potential antitrypanosomal and antimalarial agents.
abstract: The requirement for rational drug design in the search for new agents that are active against parasitic protozoa prompted our in vitro studies with a group of 9-anilinoacridines. In vitro growth assays with Trypanosoma lewisi identified a series of C-1' alkylaminoacridines which possess previously unreported potent growth-inhibitory activities against T. lewisi at a concentration range of 0.1 to 1 microM. In contrast, several 9-anilinoacridines that possess acridine ring NH2 substituents at C-3 and C-6 were inactive against T. lewisi, but they possessed strong activity against Plasmodium falciparum at a concentration range of 0.1 to 2.8 microM. In mammalian cells, amsacrine [4'-(9-acridinylamino)methanesulfon-m-anisidide] inhibits DNA topoisomerase II; however, amsacrine was only weakly active against T. lewisi. Such differences in the patterns of susceptibility of mammalian cells, T. lewisi, and P. falciparum to these 9-anilinoacridines may reflect enzyme differences between different parasites and mammalian cells that can be exploited by further improvements in drug design.
authors.affiliation: Department of Cellular Biology, University of Auckland, New Zealand.
authors.forename: D
authors.initials: D
authors.lastname: Figgitt
authors.forename: W
authors.initials: W
authors.lastname: Denny
authors.forename: P
authors.initials: P
authors.lastname: Chavalitshewinkoon
authors.forename: P
authors.initials: P
authors.lastname: Wilairat
authors.forename: R
authors.initials: R
authors.lastname: Ralph
mesh_terms: D000166:Acridines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D006801:Humans; D009115:Muridae; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014350:Trypanosoma lewisi / Q000187:drug effects*; D014352:Trypanosomiasis / Q000188:drug therapy / Q000469:parasitology
chemical_list: D000166:Acridines; D000962:Antimalarials; D000970:Antineoplastic Agents; D014344:Trypanocidal Agents