Síntese e caracterização dos 3-(benzo[c][1,2,5]calcogenodiazol-5- il)-5-(ariletinil)1,2,4-oxadiazóis derivados de (z)-n’- hidroxibenzo[c][1,2,5]calcogenodiazóis-5-carboximidamida e dos ácidos 3-arilpropiólicos

• Ano de defesa: 2023
• Autor(a) principal: Pereira, Paola Cavalheiro
• Orientador(a): Dornelles, Luciano
• Banca de defesa: Sauer, André Carpes, Schumacher, Ricardo Frederico
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Centro de Ciências Naturais e Exatas
• Programa de Pós-Graduação: Programa de Pós-Graduação em Química
• Departamento: Química
• País: Brasil
• Palavras-chave em Português: 1,2,4-oxadiazóis; 1,2,5-benzocalcogenodiazóis; Ácidos fenilpropiólicos; Docking molecular
• Palavras-chave em Inglês: 1,24-oxadiazoles; 1,2,5-benzochalcogenadiazoles; Phenylpropionic acids; Molecular docking
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/29864

The importance of heterocycle chemistry has grown in recent years, enabling the connection among many interdisciplinary areas of science, standing out in synthetic organic chemistry, mainly in the pharmaceutical area, due to its wide range of applicability in new molecular structures. Within this class, N-heterocycle compounds stand out, which have been the target of advances in studies on synthesis methodologies, as they present interesting biological profiles, with potential therapeutic activities and recent advances in materials chemistry, with promising results in optoelectronic chemistry due to the properties of luminescence and electronic delocalization which can be enhanced if conjugated to acyclic groups such as alkynes. Thus, joining the development of 1,2,4-oxadiazoles, 1,2,5- benzochalcogenodiazoles and phenylpropiolic acids, the present work sought to develop a methodology to synthesize and characterize a series of 3,5-1,2,4-oxadiazoles dissubstituted: presenting the 1,2,5-benzocalcogenodiazoles (15; 16; 17) substituted in position 3 of the 1,2,4- oxadiazole ring and an aryletynyl (21a-e) in position 5, which made it possible to obtain 14 new compounds, with high π-conjugation. To achieve this objective, a one pot synthesis was carried out, using ethyl chloroformate as activating agent and potassium carbonate as base for cyclization, in open atmosphere and reflux temperature, forming the desired products with good yields (56 - 80 %). The compounds obtained were characterized by 1H and 13C NMR and lowresolution mass spectrometry for a more detailed study of the generated fragments, and highresolution mass analysis – HRSM was also performed. Such conjugated π organic structures and containing the N-heterocycle 1,2,4-oxadiazoles as the center, linked to diferente substituents in an aromatic system through a C-C triple bond, enables future studies on the physical-chemical aspects and structural modifications of the synthesized molecules. After obtainig the compounds, they were evaluated for their antitumor activities, through a docking study using the protein tubulin, to which the in silico study of molecular anchorage at the binding site of a synthetic analogue of podophyllotoxin confirmed the interaction of the compounds obtained in this work with the protein tubulin, with valeus of favorable energies from -7,5 to -7,9 Kcal/mol. The results obtained suggest a possible mechanism for planning future studies of antitumor activity of the synthesized compounds.