Amino acid containing amphiphilic hydrogelators with antibacterial and antiparasitic activities

Abstract

Nanoscale self-assembly of peptide constructs represents a promising means to present bioactive motifs to develop new functional materials. Here, we present a series of peptide amphiphiles which form hydrogels based on β-sheet nanofibril networks, several of which have very promising anti-microbial and anti-parasitic activities, in particular against multiple strains of <i>Leishmania</i> including drug-resistant ones. Aromatic amino acid based amphiphilic supramolecular gelators C₁₄-Phe-CONH-(CH₂)_<i>n</i>-NH₂ (<i>n</i> = 6 for P1 and <i>n</i> = 2 for P3) and C₁₄-Trp-CONH-(CH₂)_<i>n</i>-NH₂ (<i>n</i> = 6 for P2 and <i>n</i> = 2 for P4) have been synthesized and characterized, and their self-assembly and gelation behaviour have been investigated in the presence of ultrapure water (P1, P2, and P4) or 2% DMSO(v/v) in ultrapure water (P3). The rheological, morphological and structural properties of the gels have been comprehensively examined. The amphiphilic gelators (P1 and P3) were found to be active against both Gram-positive bacteria <i>B. subtilis</i> and Gram-negative bacteria <i>E. coli</i> and <i>P. aeruginosa</i>. Interestingly, amphiphiles P1 and P3 containing an L-phenylalanine residue show both antibacterial and antiparasitic activities. Herein, we report that synthetic amphiphiles with an amino acid residue exhibit a potent anti-protozoan activity and are cytotoxic towards a wide array of protozoal parasites, which includes Indian varieties of <i>Leishmania donovani</i> and also kill resistant parasitic strains including BHU-575, MIL^R and CPT^R cells. These gelators are highly cytotoxic to promastigotes of <i>Leishmania</i> and trigger apoptotic-like events inside the parasite. The mechanism of killing the parasite is shown and these gelators are non-cytotoxic to host macrophage cells indicating the potential use of these gels as therapeutic agents against multiple forms of leishmaniasis in the near future.