Banca de DEFESA: JOANA DARC DA SILVA TRINDADE
Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.DISCENTE : JOANA DARC DA SILVA TRINDADE
DATA : 17/10/2019
HORA: 09:00
LOCAL: Sala 50-Pavilhão de Química
TÍTULO:
STUDIES IN THE REPOSITIONING OF THE DRUG NIMESULIDE FOR THE TREATMENT OF CHAGAS DISEASE: SYNTHESIS OF DERIVATIVES, EVALUATION OF THE TRIPANOCIDAL ACTIVITY AND INVESTIGATION ON POSSIBLE MECHANISMS OF ACTION
PALAVRAS-CHAVES:
Trypanosoma cruzi, non-steroidal antiinflammatory drugs, nitroaromatics, antiparasitic drugs, piperine, molecular hibridization
PÁGINAS: 200
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Orgânica
ESPECIALIDADE: Síntese Orgânica
RESUMO:
Chagas disease is treated only by two drugs, nifurtimox (1) and benzonidazole (2). However, these two nitroaromatic drugs are not effective in all stages of the infection. Furthermore, both drugs cause severe side effects, which justifies the search for new therapeutic alternatives to treat this serious parasitic infection. Literature data describe the interference of non-steroidal anti-inflammatory drugs on Trypanosoma cruzi trypomastigote infection process on mammalian cells. The mechanism of action of these drugs involves their action on the enzymatic cyclooxygenase complex, which is an important event for the establishment of the parasitic infection. Additionally, the toxic effects of nitro-aromatic compounds are well known and T. cruzi is greatly affected by the action of these molecules in their redox equilibrium. From this information, we proposed in this work the investigation of the trypanocidal activity of the nimesulide (3), a non-steroidal anti-inflammatory drug, which has in its structure a nitro-aromatic group. The drug repositioning approach is an important tool in the discovery of drugs applicable to the treatment of neglected diseases. Another strategy, developed in this work, involved the use of molecular hybridization strategy in the design of two nimesulide derivatives (3), hybrids of nimesulid and the trypanocidal natural amide, piperine (5). The results obtained from the biological evaluations carried out herein indicated the antiparasitic activity of nimesulide (3) on the different evolutive forms of T. cruzi. In addition, the two molecular hybrids constructed, the hybrid H1, in which the aromatic nitro portion was preserved, presented trypanocidal action, while the hybrid H2 significantly lost activity due to the absence of the nitro group. The set of results obtained in this work pointed out the nitro substituent present in the structures of both nimesulide (3) and the hybrid H1 as a pharmacophoric group on the trypanocidal activity exhibited by both, validating the hypothesis of this study.
MEMBROS DA BANCA:
Presidente - 1058758 - MARCO EDILSON FREIRE DE LIMA
Interno - 1177598 - ROSANE NORA CASTRO
Externo ao Programa - 1545840 - LUCIA HELENA PINTO DA SILVA
Externo à Instituição - ALEXANDRE MORROT - UFRJ
Externo à Instituição - JADEL MULLER KRATZ
Externo à Instituição - DEIVID COSTA SOARES - UFRJ
Externo à Instituição - WANDA PEREIRA ALMEIDA - UNICAMP