Síntese, utilizando metodologias alternativas, e avaliação citotóxica de compostos mesoiônicos da classe 1,3,4- tiadiazólio-2-amida

Abstract

Mesoionic compounds present special structures that allow several opportunities for new synthesis of heterocyclic compounds, besides the possibility of biomolecular interactions, such as DNA and proteins, which are very important factors that contribute to explain the diversified biological activities. At present, a cleaner and more efficient synthetic process has been considered especially necessary in order to respect environmental issues. Thus, in this work the 1,3,4- thiadiazolium-2-aminide mesoionic class precursors were synthesized, as hydrochloride form using the traditional methodology through anydroacylation reaction of 1,4- diphenylthiosemicarbazide in the presence of substituted acid chlorides, and also by alternative methodologies. Searching the adequate synthesis to meet the Green Chemistry concepts the mesoionic hydrochlorides were also obtained through two different methodologies from 1,4- diphenylthiosemicarbazide with the appropriate aldehyde in the presence of acid Lewis and 1,4-dioxane as organic solvent. Both methodologies used two different acid Lewis, the thionyl chloride (SOCl2) and trimethylsilyl chloride (TMS-Cl). The use of aldehyde and acid Lewis aimed to eliminate one or two steps in relation to the traditional methodology, in which the carboxylic acid and, later, the chloride acid are prepared. One of the methodologies used the microwave irradiation of the reactants for 5 minutes, while the other used ultrasound irradiation for 10 minutes. The use of these new methodologies allowed the mesoionic hydrochloride synthesis, 1,3,4-thiadiazolium-2-phenylamines, in better yields and lower reaction times when compared to the 4 hour traditional methodology; it took 5 minutes to microwave irradiation and solvent free conditions, and 10 minutes to ultrasound irradiation, in addition to the elimination of a step to benzaldehyde derivatives and two steps to cinnamaldehyde derivatives. All the compounds were characterized by spectroscopic techniques as NMR 1H, 13C and infrared. Furthermore, the cytotoxic activities of some mesoionic compounds were evaluated against HL60 and K562 human leukemia lines, and Daudi lymphoma line, showing promising results, specially to 4-phenyl-5-(4 -nitro-estyril)-1,3,4-thiadiazolium-2-phenylamine chloride derivative.