ABSTRACT
The synthesis of 1-amino-10-alkyl-9-acridinones 4 and 5 and of homologous 9-thio-acridinones 7 and 8 are described. Similarly, the synthesis of 1-nitro-4-(2'-aminoethylamino)-9-acridinones 13 and 15, is described. Compound 4 was used as starting material for the preparation of 10-alkyl-9-acridinone dimers 6, bridged with an alpha,omega-diamido chain. Compound 15 was selected for biological investigations on pathogenic parasite strains, and a promising antiamoebic activity could be shown.
Subject(s)
Acridines/chemical synthesis , Aminoacridines/chemical synthesis , Antiprotozoal Agents/chemical synthesis , Acanthamoeba/drug effects , Acridines/pharmacology , Acridines/toxicity , Aminoacridines/pharmacology , Aminoacridines/toxicity , Animals , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/toxicity , CD4-Positive T-Lymphocytes/drug effects , Leishmania donovani/drug effects , Male , Mice , Trypanosoma cruzi/drug effectsABSTRACT
New acridinonic derivatives, which are hydroxy- and methoxy-substituted in positions 1, 4, and 1,4 were prepared with a view to obtain antiparasitic drugs. These compounds were tested against Trypanosoma cruzi strains and their capability of interacalation into DNA was determined. Nucleus substitutions, DNA binding, and trypanocidal activities have been correlated.
Subject(s)
Acridines/chemical synthesis , DNA, Protozoan/drug effects , Trypanocidal Agents/chemical synthesis , Acridines/pharmacology , Animals , Cell Nucleus/drug effects , Cell Nucleus/metabolism , DNA , DNA, Protozoan/metabolism , Intercalating Agents/pharmacology , Mice , Mice, Inbred BALB C , Trypanocidal Agents/metabolism , Trypanosoma cruzi/drug effectsABSTRACT
Some acridine compounds referred to as 9-imino, 9-oxo and 9-thio derivatives were screened for activity against Trypanosoma cruzi in vitro. The results are discussed here with reference to the structure of the compounds tested. Attempts to elucidate the mode of action of active acridines are also included. The most active compounds that were tested were 9-thioacridanones and 9-thio-1,2,3,4-tetrahydroacridanones Added to this, the dialkylaminoalkylthio group seems to be the most convenient molecular moiety for trypanocidal activity in the 9-substituted acridine series.
Subject(s)
Acridines/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Drug Evaluation, PreclinicalABSTRACT
In vitro antiamebic activity of selected acridine derivatives has been investigated against Naegleria and Acanthamoeba species. The most active compounds belong to the 9-thioacridanone and the 1,2,3,4-tetrahydro-9-thioacridanone series. In addition, some structure-activity relationships are proposed.
