1.D.266. The Pyrimidine Nucleoside-treated Membrane (PNtM) Family
Nucleoside derivatives disorder membrane lipids depending on the types of nucleoside bases and membrane-forming lipids (Ostroumova et al. 2024). The 5'-norcarbocyclic uracil derivatives were found to be ineffective, while N4-alkylcytidines showed 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 revealed 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 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 (Ostroumova et al. 2024) .