Efeitos de chalconas no desenvolvimento e sistema imunológico em Aedes aegypti L. (Diptera: Culicidae)

Abstract

The mosquito Aedes aegypti L. is a vector responsible for transmitting several arboviruses, such as dengue, zika, and chikungunya. In a global context, there is a process of population expansion, partly due to the inefficiency of the control methods used. In this sense, the search for new molecules with insecticidal activity is of great importance. Chalcones are natural compounds belonging to the group of flavanoids and have become an important target for current scientific research due to their wide biological applicability. Therefore, the objectives of this study are to evaluate the effects of four different types of chalcones (CH) on the in silico activity, development, and immune system in Ae. aegypti and their toxicity in A. salina. As a methodology, the CHH were synthesized by the Organic Synthesis Laboratory (LabSíntese)-UFPB, being described as: Heterocyclic Chalcone (CHH), Chalcone Fluoride (CHF), Bromo Chalcone (BCH), and Chalcone Nitrogen (CHN). The computational analyses were performed using the software Molpredict X, Spartan14, ChemAxon, and Molegro Virtual Docker v.6.0.1. For analysis under the development phases in Ae. aegypti and toxicity in A. salina, different concentrations of CHH (2.5–1000 ppm) were used, and mortality (Mt) was evaluated in the period of 24 and 48 hours. Scanning electron microscopy (SEM) was used for morphological analysis of the eggs against exposure to CHH. For the immunological analysis of larvae (L3), the nitrite ion (NO2-) concentration and total hemocyte profile in the hemolymph pool were evaluated. In the control groups, the insects were exposed to dechlorinated water, Tween 80 and 20 at 2%. The experiments were performed in triplicate. As results, the CHH demonstrated conformational stability and lower energy than the target proteins of the study (CHN: -126,547 kcal/mol-1), and (CHH: -128,536 kcal/mol-1) respectively, when compared to the co-crystallized ligands. In the larvicidal activity, there was a higher Mt in the 48-hour period, decreasing the LC50: 10.04 ppm (24h) and 6.84 ppm (48h) for CHH; CHF: 42.01 ppm (24h) and 8.46 ppm (48h); BCH: 195.6 ppm (24h) and 161.8 ppm (48h); CHN: 595.6 ppm (24h) and 553.4 ppm (48h). In the pupicidal and adulticidal bioassays, BCH and CHN induced a higher Mt in the 24-h exposure period, with LC50 of 562.1 and 893.7 ppm, respectively. In the hatchability assay, there was a 97.4% decrease in hatching. In the SEM analysis, CHH caused visible damage to the exochorion of the eggs. CHH promoted a quantitative increase in hemocytes, CH: 9.6 ± 1.3% (24h) and 10.7 ± 8.8% (48h); ICC: 10.91 ± 1.3% (24h) and 13.7 ± 7.8% (48h); CHN: 10.7±1.5% (24h) and 11.1±7.8% (48h). On the other hand, BCH promoted a decrease of 22.3±1.3% (24h) and 16.4±1.8% (48h), but without statistical significance. An increase in NO2- was observed in all CHH (24h: 18.9±0.6% and 48h: 20.9±0.6%). In the toxicity bioassays, Mt occurred against all concentrations tested, with BCH (4.85ϻ [mean] Mt) and CHN (4.66ϻ Mt) demonstrating low toxicity in Artemia. Finally, the results stand out as CHH molecules with insecticidal and immunomodulatory activity, promising for the development of new products with potential impact on public health. However, toxicity bioassays portray their activity towards non-target organisms, which should be better evaluated in future studies.