Abstract

THE MICROBICIDAL DEFENSES INVOLVED IN INTRACELLULAR TOXOPLASMA GONDII, TRYPANOSOMA CRUZI AND LEISHMANIA AMAZONENSIS ELIMINATION IN THE PRESENCE OF SEMICARBAZONES, THIOSEMICARBAZONES, AND THIAZOLIDINONES

Laís Pessanha De Carvalho* and Edésio José Tenório De Melo

Abstract

Some pathogens that cause diseases of medical and veterinary importance settle down and utilize the intracellular environment to replicate and disseminate, which establish an infection on several vertebrate hosts. In this context, Toxoplasma gondii, Trypanosoma cruzi and Leishmania sp are obligate parasites that infect host cells of vertebrates, including humans, which cause toxoplasmosis, Chagas disease, and leishmaniasis, respectively. These parasites handle many mechanisms to evade the microbicidal defenses of the host cell that includes avoiding the endocytic pathway and lysosome fusion. The success of the parasite evasion mechanisms will allow the infection development, with the parasite within a parasitophorous vacuole or free in the cytoplasm, which limits the activity of chemotherapeutic agents. Studies about the mechanisms of parasite survival are fundamental to develop new drugs to combat the intracellular pathogens. Compounds of semicarbazone, thiosemicarbazone, and thiazolidinone classes have been extensively tested against these three parasites, and some studies showed that they were able to arrest the replication cycle of T. gondii, T. cruzi and L. amazonensis, controlling the cell infection, which allows the recovery of microbicidal defenses of host cells. Consequently, the parasites are identified and eliminated through the parasite-containing vacuole - lysosome fusion or autophagic pathway.

Keywords: Anti-proliferative drugs; intracellular parasites; Toxoplasma gondii; Trypanosoma cruzi; vacuole-lysosome fusion.