Avaliação da toxicidade de tiossemicarbazonas derivadas de benzaldeído, acetofenona e benzofenona frente a larvas de Aedes aegypti

Abstract

The thiosemicarbazones are a class of chemical compounds with broad pharmacological profile, however, there is few studies on its toxicity in insects. Currently, Aedes aegypti mosquitoes (Linnaeus, 1762) has caused public health problems due to its potential for disease dissemination, such as dengue fever, yellow fever, chikungunya and zika. The fight against the vector is one of most efficient strategies used in the control of these diseases. However, the limited number of larvicidal agents and the emergence of resistant mosquitoes can compromise this fight, which has motivated the research for new molecules that can act as larvicides. In this work, a series of fourteen thiosemicarbazones derived from benzaldehyde, acetophenone and benzophenone against Aedes aegypti larvae were evaluated. The compounds were prepared and characterized by their infrared and nuclear magnetic resonance spectra as well as its colloidal stability in 1% DMSO aqueous solution. The larvicidal activity of the compounds, at concentration range from 0.1 to 100 μM, was evaluated against larvae in the L4 stage, being that benzophenone-derived thiosemicarbazones demonstrated larvicidal activity. The swimming behavior and external and midgut cells morphology were evaluated for the active compounds. In these experiments were observed a reduction of mobility, deformity of some larvae and alterations in cells upon exposition to thiosemicarbazones. Immunofluorescence assays involving anti-phospho-histone H3, microtubule-associated protein light chain 3 antibody (anti-LC3A/B), anti-caspase 3, and anti-peroxidase antibodies were performed on midgut cells from larvae. These results highlight the cytotoxic effect of thiosemicarbazones, but without the participation of apoptotic and autophagic processes and peroxidase enzymes. The results obtained corroborate a potential larvicidal activity of thiosemicarbazones, however, the origin of its cytotoxicity should be better investigated.