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.

Author(s)

Sarah Fernandes Teixeira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2016-08-18

Examining board members

Emer Suavinho Ferro; Roger Chammas; Débora Levy; Leticia Veras Costa Lotufo

• Advisor: Emer Suavinho Ferro; Adilson Kleber Ferreira

Abstract

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. (AU)

• FAPESP's process: 14/24455-0 - Evaluation of the activity of CHY-1, a novel miltefosine analogue, as a potential CTP: phosphoethanolamine cytidylyltransferase enzyme inhibitor, against non-small cell lung câncer
• Grantee: Sarah Fernandes Teixeira
• Support Opportunities: Scholarships in Brazil - Master