m ‐Nitrocinnamic Acid Containing Lipophilic Peptide Exhibits Selective Growth Inhibition Activity against Leishmania major

A series of peptides ( 1 ‐ 3 ) containing m ‐nitrocinnamic acid, α‐aminoisobutyric acid (Aib) and L‐leucine has been synthesized and their antileishmanial propensities have been studied. The compound 1 was synthesized by condensation reaction of 3‐nitrobenzaldehyde and malonic acid. The compound 1 forms duplex by intermolecular hydrogen bonding interactions in solid state and finally self‐assemble to form supramolecular helix through C‐H⋅⋅⋅O hydrogen bonds. The peptide 2 shows antiparallel sheet‐like assembly through intermolecular N‐H⋅⋅⋅O and C‐H⋅⋅⋅O hydrogen bonding interactions. The peptide 3 adopts extended conformation and self‐assemble to form bowl‐like morphology. Moreover, the peptide 3 exhibits significant growth inhibition property on Leishmania major promastigotes with an IC 50 value of 13 μg/ml. But compound 1 and peptide 2 have IC 50 values 100 μg/ml and 41 μg/ml respectively. The higher lipophilicity of peptide 3 may increase the chances of reaching this intracellular parasite. Thus peptide 3 shows selective toxicity towards Leishmania (IC 50 =13 μg/ml) and compared to several existing standard antileishmanial drugs like pentastam (IC 50 > 64 μg/ml), sodium stibogluconate (IC 50 > 64 μg/ml) or ketoconazole (IC 50 =72 μg/ml), peptide 3 shows at least 2–6 times higher potency.