Influence of N-Methylation and Conformation on Almiramide Anti-Leishmanial Activity

The almiramide N-methylated lipopeptides exhibit promising activity against trypanosomatid parasites. A structure–activity relationship study has been performed to examine the influences of N-methylation and conformation on various strains leishmaniasis protozoan cytotoxicity. synthesis biological analysis twenty-five analogs demonstrated that derivatives with a single methyl group either first or fifth residue amide nitrogen exhibited greater than permethylated peptides relatively high potency resistant strains. Replacement amino residues in peptide, by turn inducing ? ? lactam (Agl) N-aminoimidazalone (Nai) counterparts, reduced typically anti-parasitic activity; however, peptide amides possessing Agl at second retained significant unmethylated series. Systematic effects methylation geometry indicated relevance an extended conformer about central residues, conformational mobility tertiary isomerization extremities active peptides.