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

Abstract

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 π‐π 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 11μg/ml and the Phe containing dipeptide 2 exhibits IC50 21.17μg/ml on Leishmania major promastigotes. But the Val and Gly containing dipeptides 3 and 4 have IC50 values 138.23 μg/ml and 21.75 μg/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.

1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study

“…Several authors have reported the use of different 1,2,3-triazole derivatives as potential antileishmanial agents [27][28][29]. According to our results on activity against promastigote forms, compounds 2, 4, 5, and 6 showed significant results.…”

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

“…11) has promising anti-leishmanial activity. 123 The IC 50 value calculated based on normal growth inhibition and IC 50 value of 93 on Leishmania major promastigotes was 11 μg/mL. The most relevant factors were the cytotoxicity, lipophilicity and antiparasitic activity of the lead compounds a substantial points for the design of a new anti-leishmanial agents.…”

Efficient Dimerization Disruption of Leishmania infantum Trypanothione Reductase by Triazole-phenyl-thiazoles

“…1,2,3-Triazole-containing compounds have been widely investigated because they are considered privileged scaffolds in different areas of medicinal chemistry, 36 − 38 including several examples in the antileishmanial field. 39 Interest in this molecular architecture has also been fueled by its expedient synthesis through “click chemistry”. 40 In this scenario, we decided to apply the bioisosteric replacement of imidazole by 1,2,3-triazole in our recently described imidazole-phenyl-thiazoles.…”

“…1,2,3-Triazole-containing compounds have been widely investigated because they are considered privileged scaffolds in different areas of medicinal chemistry, − including several examples in the antileishmanial field . Interest in this molecular architecture has also been fueled by its expedient synthesis through “click chemistry” .…”