Síntese, caracterização e avaliação dos potenciais citotóxico e larvicida de tiossemicarbazonas derivadas de Chalconas e seus complexos metálicos frente a mosquitos do gênero Aedes

Abstract

Mosquitoes of the Aedes genus have caused serious public health problems by acting as vectors for several arboviruses such as dengue, chikungunya and zika. The most efficient strategy to control these diseases is to combat the vector. However, the limited number of larvicidal agents and the emergence of resistant mosquitoes may compromise this fight. This has motivated the search for new molecules that can act as larvicides. Chalcones and thiosemicarbazones are classes of organic compounds that stand out for their antimicrobial and cytotoxic activities. This last class also stands out for its chelating capacity, allowing the production of complexes with the most varied pharmacological activities, and in many cases being more active than free ligands. In this work, eight thiosemicarbazones derived from chalcones and their respective copper(II) and silver(I) complexes were prepared, several of which were new. The compounds were characterized by elemental analysis, conductimetric measurements, electronic and infrared spectra and thermogravimetric analyses. The cytotoxicity of these compounds was evaluated by cell viability of murine macrophage lines RAW 264.7 and J774 A.1 and Aedes albopictus C6/36 at concentrations ranging from 0.01 to 100 µM. For selected thiosemicarbazones and Cu(II) complexes, the survival of Aedes aegypti larvae from the L4 stage to adulthood, the morphology of larval midgut cells after treatment for 24 h and caspase-3 labeling by immunofluorescence were evaluated. The Cu(II) complexes were about 10 times more cytotoxic than free thiosemicarbazones against all strains tested. For the majority of Ag(I) complexes, their cytotoxicity was not greater than that of free thiosemicarbazones, even though their salt had a cytotoxic effect at the highest concentration tested. Some of the selected compounds led to an increase in larvae mortality with damage to midgut cells, however without positive caspase-3 labeling. The results demonstrate that the strategy of complexing thiosemicarbazones with copper(II) led to an increase in cytotoxic activity and that some compounds showed promising larvicidal potential against mosquitoes of the genus Aedes.