LEISHMANIA BRAZILIENSIS : Cytotoxic, cytostatic and chemotactic effects of poly-lysine-Methotrexate-conjugates

Abstract

Chemotactic responses play a significant role duringLeishmaniadifferentiation, 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 Leish-mania. 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 poly-peptide–methotrexate conjugates depends on specific chemical characteristics. For example, the N-ter-minal 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-orc-carboxylic groups) affect their chemotactic activity. Specific cytotoxic activities and cytostatic effects of the conju-gates 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-Leishmaniasubstances acting selectively on Leishmaniaand different hosts