Leishmania braziliensis: Cytotoxic and chemotactic effects of branched chain polypeptide conjugates with poly [L-Lysine] backbone

Abstract

Chemotactic responses play a significant role during Leishmania differentiation, as well as in the course of parasite–host–cell interaction, a process that precedes a successful infection. The present study uses the modified ‘‘two-chamber capillary assay’’ to quantitatively evaluate the chemotactic properties and the toxic activities of methotrexate containing branched chain polymeric polypeptide conjugates in Leishmania. Our results demonstrate that this methodology quantitatively determines the taxis of Leishmania towards/against gradients of compounds. They also demonstrate that chemotaxis produced by the polypeptide– methotrexate conjugates depends on specific chemical characteristics. For example, the N-terminal amino acid (Ser or Glu) location at the branch significantly influences the elicited chemotaxis. Furthermore, the use of different attachment sites in the methotrexate conjugates (a- or c-carboxylic groups) affect their chemotactic activity. Specific cytotoxic activities and cytostatic effects of the conjugates on parasites and on murine and human cells of the macrophage/monocyte system respectively, suggest that these ligands may be used as a group of anti-Leishmania substances acting selectively on Leishmania and different hosts.