Síntese, Avaliação Biológica e Estudos in silico de Adutos de Morita-Baylis-Hillman frente ao Aedes aegypti

Abstract

Currently, pathogens that have adapted to the changes imposed by nature continue to cause extensive socioeconomic damage and, especially, to human health. One example is the Neglected Tropical Diseases caused by viruses, such as Dengue, Zika, and Chikungunya. These arboviruses, in turn, emerge from zoonotic cycles, mostly transmitted by the arthropod Aedes aegypti, where for Zika and Chikungunya no vaccine is available yet. Although there is a vaccine for some serotypes of Dengue, the high expansion of the vector has caused increasing levels of this disease in epidemic cycles every 3 to 5 years. Therefore, this work aimed to contribute to the design and development of molecules with potential biological action against the vector Aedes aegypti through the Morita-Baylis-Hillman (MBH) reaction methodology and in silico studies to understand the possible mode of action of such compounds. Thus, the results of the synthesis presented satisfactory yields, with the compounds being later submitted to larvicidal evaluation, together with some MBH adducts that were available through a partnership with an external research group. Among these, 3 showed promising activity, especially methyl 2-([1,1'-biphenyl]-4-yl(hydroxy)methyl)acrylate (3n). Furthermore, molecular docking studies were conducted with the enzyme AaAChE, the main biological target in vetor control, and other possible biological targets, suggesting a possible multiple action. However, morphological analyses suggest probable damage in organs in the thorax region responsible for the synthesis of the peritrophic membrane, an essential component of the insect defense system. Thus, a degenerative response was observed in the epithelial tissue in the abdomen region of the larva. In summary, it is evident that MBH adducts are a promising class of compounds in the population control of Aedes aegypti.