P14-01 Initial cytogenotoxic screening of N-tosylindole, a new larvicide against Aedis aegypti, the transmitter of Dengue, Chicungunya and Zika

Aedes aegypti is the mosquito that transmits Dengue, Chikungunya, Zika and yellow fever, diseases that affect millions of people around the world, killing thousands. Over the years, A. aegypti larvae have developed resistance to currently used larvicides, being the development of new larvicides of fundamental importance. In this context, N-tosylindole was developed, an indole derivative whose recent studies have shown great larvicidal activity against A. aegypti larvae. As this compound must be used in water tanks, it is essential to analyze its toxicity. The aim of this study was to investigate the cytotoxic and genotoxic potential of N-tosylindole in cultured human peripheral blood leukocytes and human hepatoma cell line HepG2/C3A cells, and its mutagenic potential in bacterium strains. Cytotoxicity of N-tosilindole and its solubilizer polyvinylpyrrolidone (PVP) was evaluated by trypan blue staining and resazurin assay. The genotoxicity was assessed by comet assay, chromosome alterations by the cytokinesis-block micronucleus test, and genetic mutations by the AMES test. At concentrations between 1 and 200 µg/ml, N-tosylindole and its respective solubilizing control did not cause a decrease in cell viability on both cells. The genotoxicity analysis by the comet assay showed that, at concentrations of 10, 20 and 50 µg/ml, the larvicide did not produce DNA damage. Likewise, the micronucleus test did not show clastogenic/aneugenic effects or cell divising disturbance by the cytokinesis-block proliferation index (CBPI). Preliminary data using five strains of Salmonella typhimurium also did not show the occurrence of gene mutation. Considering that N-tosylindole produces a larvicidal effect at low concentrations (LC50 0.244 µg/ml), the data obtained, under the experimental conditions employed, reveal that the new larvicidal agent did not produce cytotoxic or genotoxic/mutagenic effects in leukocytes, HepG2/C3A human cells, and S. typhimurium cells. The data obtained encourage studies seeking to develop a formulation with N-tosylindole to be used in water tanks by health services and the general population, aiming to control the proliferation of mosquitoes and the transmission of Dengue, Chikungunya, Zika and yellow fever.