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Master's Dissertation
DOI
10.11606/D.42.2016.tde-11112016-101931
Document
Author
Full name
Sarah Fernandes Teixeira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Ferro, Emer Suavinho (President)
Chammas, Roger
Levy, Débora
Lotufo, Leticia Veras Costa
Title in Portuguese
Avaliação da atividade do CHY-1, um novo análogo da miltefosina, como potencial inibidor da enzima CTP: fosfoetanolamina-citidilil-transferase, sobre o carcinoma de pulmão de não-pequenas células.
Keywords in Portuguese
Carcinoma de pulmão de não-pequenas células (CPNPC)
Citotoxicidade
CTP: fosfoetanolamina-citidilil-transferase (Pcyt2)
Morte imunogênica
Abstract in Portuguese
O câncer de pulmão é um dos mais incidentes e letais, e, assim, a busca de novos fármacos é necessária. Atualmente o desenvolvimento de fármacos conta com abordagens computacionais que otimizam este processo. Dado que a fosfatidiletanolamina desempenha importantes papeis fisiológicos e uma das enzimas envolvidas na sua síntese, a CTP:fosfoetanolamina-citidilil-transferase (Pcyt2) é frequentemente superexpressa em células de câncer de pulmão, no presente trabalho, foram avaliados o potencial terapêutico de CHY-1, um análogo da miltefosina desenvolvido como inibidor da enzima Pcyt2, e os mecanismos inerentes à sua atividade antitumoral. O CHY-1 apresentou citotoxicidade superior ao seu protótipo e a outro inibidor da enzima Pcyt2, a meclizina. Além disso, as células malignas foram mais sensíveis ao CHY-1 do que as células não-tumorigênicas. Em conclusão, o presente trabalho evidencia o potencial do CHY-1 como um inibidor da enzima Pcyt2 e candidato a fármaco com atividade preferencial para câncer de pulmão.
Title in English
Evaluation of the activity of CHY-1, a novel miltefosine analogue, as a potential CTP: phosphoethanolamine cytidylyltransferase enzyme inhibitor against non-small cell lung cancer.
Keywords in English
CTP: phosphoethanolamine cytidylyltransferase (Pcyt2)
Cytotoxicity
Immunogenic cell death
Non-small cell lung cancer (NSCLC)
Abstract in English
Lung cancer is one of the most incident and lethal cancers, thus, the pursuit for new drugs is necessary. Nowadays, new drugs development has computational tools that improves this process. Once that phosphatidylethanolamine plays several important physiological roles and one of the enzymes of its production pathway, CTP:phosphoethanolamine cytidylyltransferase (Pcyt2), is usually overexpressed in lung cancer cells, therefore, this study aimed was to evaluate the antitumor effects of CHY-1, a miltefosine analogue developed as an inhibitor of Pcyt2 enzyme, and to investigate the mechanisms related to its antitumor action. CHY-1 was more cytotoxicity than its prototype, miltefosine, and was more cytotoxic than another inhibitor Pcyt2 enzyme, meclizine. Morevover, malignant cells were more sensitive to CHY-1 effects than non-tumorigenic cells. In conclusion, this work presents CHY-1 as an inhibitor of Pcyt2 enzyme and new candidate a drug with preferential activity on NSCLC cells.
 
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Release Date
2018-11-11
Publishing Date
2016-11-11
 
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