Leishmania braziliensis: Cytotoxic, cytostatic and chemotactic effects of poly-lysine-methotrexate-conjugates

Emilia Díaz, László Köhidai, Arturo Ríos, Oriana Vanegas, Adrian Silva, Rita Szabó, Gábor Mezo, Ferenc Hudecz, Alicia Ponte-Sucre

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 (α- or γ-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.

Original languageEnglish
Pages (from-to)134-141
Number of pages8
JournalExperimental Parasitology
Volume135
Issue number1
DOIs
Publication statusPublished - Sep 1 2013

Keywords

  • Branched chain polymeric polypeptides
  • Chemotaxis
  • Leishmania
  • Methotrexate
  • Two-chamber capillary assay

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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