Derivatives of Pyrimidine Nucleosides Affect Artificial Membranes Enriched with Mycobacterial Lipids.
Pharmaceutics
; 16(9)2024 Aug 23.
Article
em En
| MEDLINE
| ID: mdl-39339148
ABSTRACT
The mechanisms of action of pyrimidine nucleoside derivatives on model lipid membranes of various compositions were studied. A systematic analysis of the tested agents' effects on the membrane physicochemical properties was performed. Differential scanning microcalorimetry data indicated that the ability of nucleoside derivatives to disorder membrane lipids depended on the types of nucleoside bases and membrane-forming lipids. The 5'-norcarbocyclic uracil derivatives were found to be ineffective, while N4-alkylcytidines demonstrated the most pronounced effects, significantly decreasing the dipalmitoylphosphocholine melting temperature and cooperativity of phase transition. The elongation of hydrophobic acyl radicals potentiated the disordering action of N4-alkylcytidines, while an increase in hydrophilicity due to replacing deoxyribose with ribose inhibited this effect. The ability of compounds to form transmembrane pores was also tested. It was found that 5-alkyluridines produced single, ion-permeable pores in phosphatidylglycerol membranes, and that methoxy-mycolic acid and trehalose monooleate potentiated the pore-forming activity of alkyloxymethyldeoxyuridines. The results obtained open up perspectives for the development of innovative highly selective anti-tuberculosis agents, which may be characterized by a low risk of developing drug resistance due to the direct action on the membranes of the pathogen.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Pharmaceutics
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Federação Russa
País de publicação:
Suíça