Synthesis and antileishmanial activities of 4,5-di-substituted acridines as compared to their 4-mono-substituted homologues
| Autor: | Nikoyan Anna, Jean Séverine, Timon-David Pierre, De Meo Michel, Dumenil Gérard, Galy Jean-Pierre, Chiron Julien, Di Giorgio Carole, Delmas Florence |
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| Rok vydání: | 2005 |
| Předmět: |
Stereochemistry
medicine.drug_class Clinical Biochemistry Pharmaceutical Science Carboxamide Biochemistry Chemical synthesis Monocytes Cell Line chemistry.chemical_compound Parasitic Sensitivity Tests Species Specificity Drug Discovery medicine Animals Humans Hydroxymethyl Amastigote Molecular Biology Cell Proliferation Leishmania biology Dose-Response Relationship Drug Molecular Structure Macrophages Organic Chemistry Biological activity biology.organism_classification Mechanism of action chemistry Acridine Molecular Medicine Acridines medicine.symptom |
| Zdroj: | Bioorganicmedicinal chemistry. 13(19) |
| ISSN: | 0968-0896 |
| Popis: | Newly synthesized 4,5-di-substituted acridines were assessed for in vitro antileishmanial activities as compared to those of their 4-mono-substituted homologues. Mono-substituted acridines exhibited a weak specificity for Leishmania parasites. Di-substituted acridines, on the contrary, displayed interesting amastigote-specific activities through a mechanism of action that might not involve intercalation to DNA. This antileishmanial property, associated with a low antiproliferative activity towards human cells, led to the identification of a new class of promising acridine derivatives such as 4,5-bis(hydroxymethyl)acridine with a nonclassical mechanism of action based on the inhibition of Leishmania internalization within macrophages. In the meantime, the effects of experimental lighting on the biological properties of acridines were assessed: experimental lighting did not significantly improve the antileishmanial activity of the compounds since it produced a greater toxicity against human cells. |
| Databáze: | OpenAIRE |
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