ABSTRACT
Synthesis and antiparasitic activity vs T. cruzi and L. donovani of a series of 9-thioaryl acridines are reported. A convenient correlation between molecular structure and biological activity is proposed. Results not only agree with the classical interactions of acridines with DNA but also suggest possible role of charge transfer complexes.
Subject(s)
Trypanocidal Agents/chemical synthesis , Trypanosoma/drug effects , Acridines/chemical synthesis , Acridines/pharmacology , Animals , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Quantitative Structure-Activity Relationship , Trypanocidal Agents/pharmacologyABSTRACT
The synthesis of several acridinic thioethers is described. Compounds prepared were tested in vitro as potential drugs against the opportunistic infection known as cryptosporidiosis. With a view to predict activity, the quantitative structure-activity relationships were investigated. Correlations between experimental data and either log P or pKa are discussed.
Subject(s)
Acridines/chemical synthesis , Coccidiostats/chemical synthesis , Cryptosporidium parvum/drug effects , Acridines/pharmacology , Acridines/therapeutic use , Animals , Animals, Newborn , Cattle , Cell Line , Coccidiostats/pharmacology , Coccidiostats/therapeutic use , Cryptosporidiosis/drug therapy , Cryptosporidiosis/parasitology , Cryptosporidium parvum/growth & development , Feces/parasitology , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Structure-Activity RelationshipABSTRACT
A set of 9-thioalkylacridinones, has been prepared and investigated "in vitro" against T. cruzi. Structure-antiparasitic activity relationships are detailed with a view to identify the major structural parameters for the activity under consideration.
Subject(s)
Acridines/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Acridines/chemistry , Acridines/classification , Animals , Antiprotozoal Agents , In Vitro Techniques , Mice , Structure-Activity Relationship , Trypanocidal Agents/chemistryABSTRACT
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.
