Síntese de novas bases de Mannich contendo os núcleos naftoquinônico, pirimidínico, ferrocênico e triazólico com atividade anticâncer

• Ano de defesa: 2021
• Autor(a) principal: Antoniazi, Mariana Klein
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Química; Centro de Ciências Exatas; UFES; Programa de Pós-Graduação em Química
• Palavras-chave em Português: Câncer; hibridação molecular; ferroceno; pirimidina; naftoquinona; subject.br-rjbn; Química
• Link de acesso: http://repositorio.ufes.br/handle/10/15576

One of the obstacles commonly faced in anticancer chemotherapy is Multiple Drug Resistance (MDR), an intrinsic or acquired resistance during the use of chemotherapy. The body's lack of response to medication makes it difficult to treat the disease. Thus, molecular hybridization (synthetic strategy aimed at the synergism of different groups of pharmacophores) is used in the synthesis of new drugs, increasing the therapeutic effectiveness of the hybrid when compared to individual cores, which can result in compounds of great value, with potential activity due to the possible synergism of the different cores incorporated in the same structure. Based on this, new molecular hybrids with potential anticancer activity containing ferrocene, pyrimidine and naphthoquinone cores in a single structure were synthesized and characterized in order to evaluate their activity against cancer cells. Initially, four -unsaturated ketones 42-45 were synthesized through the ClaisenSchmidt condensation reaction. Subsequently, through the chalcones, four 2- aminopyrimidines 47-50 were obtained by Biginelli reaction modified by Atwal. The synthesis of target molecules, the molecular hybrids, it was performed via the multicomponent Mannich reaction. We also evaluated the anticancer activity of 2-aminopyrimidines containing the ferrocene core, as well as of Mannich adducts against tumor lines SNB-19 (Astrocytoma), HCT-116 (Colon carcinoma - human), PC3 (Prostate carcinoma) and HL60 (Promyelocytic Leukemia). Of the 2-aminopyrimidine compounds containing the ferrocene core, the 48 structure obtained better results against the HCT116 and HL60 cancer strains with IC50 of 102.1 and 3.98 M respectively. Structure 50, on the other hand, showed the best result compared to the PC3 cancer lineage, with an IC50 value of 96.4 M. Of the synthesized target molecules, the hybrids 22, 23 and 26 showed a reduction in cell viability when compared to their respective 2-aminopyrimidine in the HCT116 cancer lineage. In the case of PC3 and SNB19 lineage, the Mannich adducts 22 and 23 showed an improvement in antiproliferative activity when compared to their respective 2-aminopyrimidine.