S?ntese e avalia??o da atividade biol?gica de compostos mesoi?nicos da classe dos 1,3,4-tiadiaz?lio-2-arilaminidas

• Autor(a) principal: Lopes, Nat?lia Drumond
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRRJ
• Texto Completo: https://tede.ufrrj.br/jspui/handle/jspui/4888
• topic: Cloridratos mesoi?nicos; Enzima tirosinase; Atividade citot?xica; Mesoionic compounds; Tyrosinase enzyme; Cytotoxic activity; Qu?mica

Cancer is a public health problem, being considered the second largest cause of death in Brazil. Currently, the therapeutic methods used against cancer are based on surgery, radiotherapy and chemotherapy. Although chemotherapy has been being improved recently, several types of cancer still do not have systemic and adequate treatment, such as melanoma and leukemia adult T-cell lymphoma, making it necessary to find new, more efficient and less toxic antineoplastic agents for healthy cells in order to improve the effectiveness of treatment of these diseases. Considering this scenery, heterocyclic compounds are shown to be promising substances for antitumor activity, including mesoionic compounds. In this work the synthesis of 4 series of mesoionic compounds of the class 1,3,4-thiadiazolium-2-arylaminide in the form of hydrochlorides is presented, resulting in 24 compounds in total, of which 20 are unpublished. The synthesis methodology for the serie I was oriented from the principles of Green Chemistry, performing reactions in absence of solvent and use of microwaves from piperonal derivatives and substituted thiosemicarbazides in yields between 60 and 95%. The compounds of series II, III and IV were obtained from chlorides of substituted cinnamic acids and thiosemicarbazides also substituted in 1,4-dioxane under reflux in satisfactory yields. All synthesized compounds were characterized by IR, 1H and 13C NMR spectroscopic techniques confirming the proposed structures. The compounds of series I were evaluated for inhibition of the enzyme tyrosinase, a biological marker for melanomas. The results obtained were promising for tyrosinase inhibitory activity for derivatives 16 (IC50 = 124 ?mol L-1) and 17 (IC50 = 358 ?mol L-1). The study of interaction with human serum albumin, as well as molecular modeling studies, were performed for these compounds justifying the results obtained in vitro. The compounds of series II were evaluated for cytotoxic activity against three human leukemia lines (Jurkat, MT2 and K562) showing good results for compounds 18 and 22, whereas the assays for the other compounds are in progress with promising preliminary results. The results obtained in this thesis indicate that mesoionic compounds can be used as prototypes for new agents in cancer chemotherapy.