Síntese, caracterização e atividade anticâncer de hidrazino carbotioamidas e compostos mesoiônicos da classe 1,3,4-tiadiazólio-2-aminidas

Pereira, Danilo Sousa

Please use this identifier to cite or link to this item: https://rima.ufrrj.br/jspui/handle/20.500.14407/17704

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DC Field	Value	Language
dc.contributor.author	Pereira, Danilo Sousa	-
dc.date.accessioned	2024-08-09T15:14:15Z	-
dc.date.available	2024-08-09T15:14:15Z	-
dc.date.issued	2019-03-29	-
dc.identifier.citation	PEREIRA, Danilo Sousa. Síntese, caracterização e atividade anticâncer de hidrazino carbotioamidas e compostos mesoiônicos da classe 1,3,4-tiadiazólio-2-aminidas. 2019. 200 f. Tese (Doutorado em Química, Ciências Exatas). Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica, 2019.	pt_BR
dc.identifier.uri	https://rima.ufrrj.br/jspui/handle/20.500.14407/17704	-
dc.description.abstract	O câncer é o nome dado a um conjunto de doenças que têm em comum o crescimento desordenado de células agressivas que poderão originar tumores e espalhar-se pelo corpo. É um dos principais problemas de saúde pública e necessita da contínua observação e estudo do cenário ao longo do tempo a fim de obter programas eficientes de sua prevenção e controle. Vários tipos de cânceres ainda não respondem adequadamente aos tratamentos disponíveis, tornando-se necessário alternativas para os tratamentos existentes, como na quimioterapia, onde a procura por novos agentes antineoplásicos se faz constante. Neste presente trabalho é apresentada a síntese de uma série de hidrazino-carbotioamidas e de três séries de cloridratos mesoiônicos da classe 1,3,4-tiadiazólio-2-aminida visando o estudo desses compostos frente a enzima tirosinase e, linhagens de células cancerígenas de fígado, osso e sangue. Foram sintetizados 39 compostos no total, sendo nove ainda inéditos. O estudo das metodologias de síntese foi realizado visando o uso de princípios da Química Verde para a obtenção dos compostos, sendo as hidrazino-carbotioamidas e compostos mesoiônicos obtidos em rendimentos satisfatórios. Todos os compostos sintetizados tiveram suas estruturas propostas caracterizadas via técnicas espectroscópicas de IV e RMN de 1H e 13C. As hidrazino carbotioamidas foram avaliadas quanto à inibição da tirosinase, enzima envolvida na formação de melanomas. Os resultados obtidos indicaram que os compostos 16 (IC50 = 56,50 mol L-1 ) e 17 (IC50 = 22,60 mol L-1 ) são promissores quanto à atividade inibitória da tirosinase. Os estudos de modelagem molecular bem como a interação com a soroalbumina humana confirmaram os resultados obtidos in vitro. Sais mesoiônicos sintetizados foram avaliados quanto a atividade citotóxica frente a três linhagens de leucemias humanas (C91, MT2 e Jurkat, sendo as duas primeiras infectadas com o vírus HTLV-1), uma linhagem de osteossarcoma (MG-63) e uma de hepatocarcinoma (HepG2), mostrando bons resultados. Os resultados obtidos neste trabalho de tese indicam que as hidrazino-carbotioamidas e sais mesoiônicos podem ser promissores enquanto agentes na quimioterapia do câncer.	pt_BR
dc.description.sponsorship	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES	pt_BR
dc.language	por	pt_BR
dc.publisher	Universidade Federal Rural do Rio de Janeiro	pt_BR
dc.subject	Hidrazino-Carbotioamida	pt_BR
dc.subject	Cloridrato Mesoiônico	pt_BR
dc.subject	Enzima Tirosinase	pt_BR
dc.subject	HTLV-1	pt_BR
dc.subject	Atividade Citotóxica	pt_BR
dc.subject	Câncer	pt_BR
dc.subject	Hydrazine-carbothioamides	pt_BR
dc.subject	mesoionic hydrochloride	pt_BR
dc.subject	tyrosinase enzyme	pt_BR
dc.subject	cytotoxic activity	pt_BR
dc.subject	cancer	pt_BR
dc.title	Síntese, caracterização e atividade anticâncer de hidrazino carbotioamidas e compostos mesoiônicos da classe 1,3,4-tiadiazólio-2-aminidas	pt_BR
dc.title.alternative	Synthesis, characterization and anticancer activity of hydrazine-carbothioamides and mesoionic compounds of 1,3,4-thiadiazolium-2-aminide class	en
dc.type	Tese	pt_BR
dc.description.abstractOther	Cancer is the name given to a set of diseases that have in common the disorderly growth of aggressive cells that can originate tumors and spread throughout the body. It is one of the main public health problems and needs continuous observation and study of the scenario over time in order to get programs efficient of prevention and control of cancer. Several types of cancers still do not adequately respond to the available treatments, being necessary new alternatives for existing treatments, such as chemotherapy, where the demand for new antineoplastic agents is constant. In this work the synthesis of a series of hydrazine carbothioamides and of three series of mesoionic hydrochlorides of Class 1,3,4-thiadiazolium 2-aminide aiming the study of these compounds against the enzyme tyrosinase and, strains of cancer cells of liver, bone and blood is presented. 39 compounds were synthesized in total, of which 9 are unpublished. The study of synthesis methodologies was carried out aiming at the use of green chemistry principles to obtain the compounds. The hydrazine-carbothioamides and mesoionic compounds did obtained in satisfactory yields. All synthesized compounds had their proposed structures characterized via spectroscopic techniques of IR and NMR 1H and 13C. Hydrazine-carbothioamides were evaluated for the inhibition of tyrosinase, an enzyme involved in the formation of melanomas. The results obtained indicated what the compounds 16 (IC50 = 56.50 µmol L-1 ) and 17 (IC50 = 22.60 µmol L-1 ) are promising inhibitory activity of tyrosinase. The study of molecular modelling well as of interaction with the Human Serum Albumin confirmed the results obtained in vitro. Synthesized mesoionic salts were evaluated for cytotoxic activity in the face of three human leukemia lines (C91, MT2 e Jurkat, being the first two infected with the virus HTLV-1), an osteosarcoma line (MG-63) and one of hepatocarcinoma (HepG2), showing good results. The results obtained in this work indicate that hydrazinecarbothioamides and mesoionic salts may be promising as agents in cancer chemotherapy.	pt_BR
dc.contributor.advisor1	Lima, Aurea Echevarria Aznar Neves	-
dc.contributor.advisor1Lattes	http://lattes.cnpq.br/1879077396134052	pt_BR
dc.contributor.advisor-co1	Silva, Ana Paula Pereira da	-
dc.contributor.advisor-co1Lattes	-	pt_BR
dc.contributor.referee1	Lima, Aurea Echevarria Aznar Neves	-
dc.contributor.referee1Lattes	http://lattes.cnpq.br/1879077396134052	pt_BR
dc.contributor.referee2	Pinheiro, Luiz Carlos da Silva	-
dc.contributor.referee2ID	https://orcid.org/0000-0002-6398-7717	pt_BR
dc.contributor.referee2Lattes	http://lattes.cnpq.br/5040259412514046	pt_BR
dc.contributor.referee3	Oliveira, Ana Carolina Leal de	-
dc.contributor.referee3ID	https://orcid.org/0000-0002-2556-3446	pt_BR
dc.contributor.referee3Lattes	http://lattes.cnpq.br/8605329529253229	pt_BR
dc.contributor.referee4	Marra, Roberta Katlen Fusco	-
dc.contributor.referee4Lattes	http://lattes.cnpq.br/0899105923944274	pt_BR
dc.contributor.referee5	Graebin, Cedric Stephan	-
dc.contributor.referee5ID	https://orcid.org/0000-0003-1410-1227	pt_BR
dc.contributor.referee5Lattes	http://lattes.cnpq.br/4900857097448760	pt_BR
dc.creator.Lattes	http://lattes.cnpq.br/3095391105042187	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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