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| Campo DC | Valor | Lengua/Idioma |
|---|---|---|
| dc.contributor.author | Barbosa, Igor Resendes | - |
| dc.date.accessioned | 2025-11-27T20:07:14Z | - |
| dc.date.available | 2025-11-27T20:07:14Z | - |
| dc.date.issued | 2025-10-23 | - |
| dc.identifier.citation | BARBOSA, Igor Resendes. Síntese e Avaliação Biológica de Compostos Mesoiônicos, Chalconas-Tiossemicarbazonas e Ftalazinonas, 2025, 524 f. Tese (Doutorado em Química) - Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica, 2025. | pt_BR |
| dc.identifier.uri | https://rima.ufrrj.br/jspui/handle/20.500.14407/24133 | - |
| dc.description.abstract | Nesta tese, diferentes classes de compostos foram desenvolvidas, caracterizadas e avaliadas quanto a sua atividade frente a doenças inflamatórias, virais e neoplásicas. No primeiro capítulo, híbridos sulfonamidas-sidnonas foram preparados e investigados quanto à sua atividade anti-inflamatória e antiviral. Foram capazes de reduzir a inflamação em modelo animal de lesão pulmonar aguda e inibiram a replicação do SARS-CoV-2 em células Calu-3, exibindo baixa citotoxicidade contra células não infectadas. A caracterização dos compostos foi conduzida por técnicas espectroscópicas de rotina (IV, RMN de 1H e 13C), espectrometria de massas de alta resolução, difração de raios-x e CLAE. Estudos in sílico sugerem que, de maneira geral, a classe possuí propriedades farmacocinéticas adequadas e as moléculas podem ser consideradas como bons protótipos de fármacos. Estudos físico-químicos revelaram que essas substâncias interagem fortemente com a albumina sérica humana, o que pode ocasionar longo tempo de retenção na corrente sanguínea. No segundo capítulo, foram investigadas substâncias com potencial atividade antitumoral. Inicialmente, 25 tiossemicarbazonas derivadas de chalconas e azachalconas foram sintetizadas e oito delas foram testadas contra células derivadas de hepatocarcinoma humano (Huh-7), destacando-se os derivados de azachalconas pela elevada potência – IC50 em nanomolar –, associada a complexação com íons cobre no meio celular. Na sequência, um complexo de zinco obtido a partir de uma chalcona-tiossemicarbazona foi preparado e avaliado contra células de leucemia/linfoma de células T do adulto (ATLL), causando apoptose, sem associação aparente com a geração de espécies reativas de oxigênio. Em seguida, uma série de ftalazinonas foi investigada contra células Huh-7. Uma delas, um híbrido ftalazinona-feniltiazol (A3), mostrou atividade promissora, afetando a função mitocondrial das células tratadas. Docagem molecular e cálculos semi-empíricos indicam que essa substância é capaz de interagir com a proteína pró-apoptótica Bax, sugerindo um possível mecanismo de ação para a A3. Por fim, o sal mesoiônico MI-D foi avaliado pela primeira vez em células de glioblastoma humano, tendo apresentado resultados relevantes. | pt_BR |
| dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES | pt_BR |
| dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro - FAPERJ | pt_BR |
| dc.language | por | pt_BR |
| dc.publisher | Universidade Federal Rural do Rio de Janeiro | pt_BR |
| dc.subject | câncer | pt_BR |
| dc.subject | inflamação | pt_BR |
| dc.subject | SARS-Cov-2 | pt_BR |
| dc.subject | cancer | pt_BR |
| dc.subject | inflammation | pt_BR |
| dc.title | Síntese e Avaliação Biológica de Compostos Mesoiônicos, Chalconas-Tiossemicarbazonas e Ftalazinonas | pt_BR |
| dc.title.alternative | Synthesis and Biological Evaluation of Mesoionic Compounds, Chalcone-Thiosemicarbazones and Phthalazinones | en |
| dc.type | Tese | pt_BR |
| dc.description.abstractOther | In this thesis, different classes of compounds were developed, characterized, and evaluated for their activity against inflammatory, viral, and neoplastic diseases. In the first chapter, sulfonamide-sydnones hybrids were prepared and investigated for their anti- inflammatory and antiviral activity. They were able to reduce inflammation in an animal model of acute lung injury and inhibited SARS-CoV-2 replication in Calu-3 cells, exhibiting low cytotoxicity against uninfected cells. The synthesis and characterization of the compounds were conducted through routine spectroscopic techniques (IR, 1H and 13C NMR), high-resolution mass spectrometry, X-ray diffraction, and HPLC. In silico studies suggest that, overall, the class possesses adequate pharmacokinetic properties and can be considered good drug prototypes. Physicochemical studies revealed that these substances interact strongly with human serum albumin, which may result in prolonged retention time in the bloodstream. In the second chapter, substances with potential anticancer activity were investigated. Initially, 25 thiosemicarbazones derived from chalcones and azachalcones were synthesized and eight of them were tested against human hepatocellular carcinoma derived cells (Huh-7). The azachalcone derivatives stood out for their high potency – IC50 in the nanomolar range – associated with complexation with copper ions in the cellular medium. Subsequently, a zinc complex obtained from a chalcone-thiosemicarbazone was prepared and evaluated against adult T-cell leukemia/lymphoma (ATLL) cells, causing apoptosis without apparent association with the generation of reactive oxygen species. Subsequently, a series of phthalazinones was investigated against Huh-7 cells. One of them, a phthalazinone-phenylthiazole hybrid (A3), showed promising activity, affecting the mitochondrial function of the treated cells. Molecular docking and semi-empirical calculations indicate that this substance can interact with the pro- apoptotic protein Bax, suggesting a possible mechanism of action for A3. Finally, the mesoionic salt MI-D was evaluated for the first time in human glioblastoma cells, yielding relevant results. | en |
| dc.contributor.advisor1 | Lima, Aurea Echevarria Aznar Neves | - |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/1879077396134052 | pt_BR |
| dc.contributor.advisor-co1 | Sant'Anna, Carlos Mauricio Rabello de | - |
| dc.contributor.advisor-co1Lattes | http://lattes.cnpq.br/2087099684752643 | pt_BR |
| dc.contributor.referee1 | Lima, Aurea Echevarria Aznar Neves | - |
| dc.contributor.referee1Lattes | http://lattes.cnpq.br/1879077396134052 | pt_BR |
| dc.contributor.referee2 | Kümmerle, Arthur Eugen | - |
| dc.contributor.referee2Lattes | http://lattes.cnpq.br/5598000938584486 | pt_BR |
| dc.contributor.referee3 | Carvalho, Mario Geraldo de | - |
| dc.contributor.referee3ID | https://orcid.org/0000-0001-5805-734X | pt_BR |
| dc.contributor.referee3Lattes | http://lattes.cnpq.br/9794451665032168 | pt_BR |
| dc.contributor.referee4 | Souza, Marcos Vinicius de | - |
| dc.contributor.referee4Lattes | http://lattes.cnpq.br/9936947815287310 | pt_BR |
| dc.contributor.referee5 | Lopes, Natália Drumond | - |
| dc.contributor.referee5Lattes | http://lattes.cnpq.br/4737360142654031 | pt_BR |
| dc.creator.Lattes | http://lattes.cnpq.br/3429335081089067 | pt_BR |
| dc.publisher.country | Brasil | pt_BR |
| dc.publisher.department | Instituto de Química | pt_BR |
| dc.publisher.initials | UFRRJ | pt_BR |
| dc.publisher.program | Programa de Pós-Graduação em Química | pt_BR |
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