Potential Antileishmanial Activity of a Triazole-Based Hybrid Peptide against Leishmania major

The dipeptides 1-4 with a triazole containing synthetic amino acid and Leu/ Phe/ Val/ Gly have been designed and synthesized as a potent antileishmanial agent. The 1-(2-Amino-phenyl)-1H-[1,2,3] triazole-4-carboxylic acid was synthesized using click chemistry approach. From X-ray crystallography, the peptide 1 containing a Leu residue at C-terminus adopts kink like structure but there is no intramolecular hydrogen bond. So, the hydrogen bonding sites are free and allowed for intermolecular interaction with the guests. The phenylalanine analogue 2 where the phenyl and triazole rings are perpendicular to each other also form supramolecular column-like structure through - stacking interaction. The incorporation of a triazole containing synthetic amino acid at the N-terminus enhances its anti-parasites activity. The properties such as lipophilicity and cytotoxicity, are relevant factors for the design of new antileishmanial agent. IC50 value were calculated for dipeptides 1-4 using normal growth inhibition strategy. For dipeptide 1, IC50 value is 11 mu g/ml and the Phe containing dipeptide 2 exhibits IC50 21.17 mu g/ml on Leishmania major promastigotes. But the Val and Gly containing dipeptides 3 and 4 have IC50 values 138.23 mu g/ml and 21.75 mu g/ml respectively. The higher lipophilicity of dipeptide 1 is likely to improve the chances of reaching this intracellular parasite. The experimental result show that the triazole-based dipeptide 1 is promising as antileishmanial agent.