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

Abstract

Lung cancer is one of the most incident and lethal cancers in Brazil and all over the world, thus, the pursuit for new drugs to control this disease is necessary. Among the tumor cellular changes there are the high proliferative activity level and the consequent cellular membrane continuous and increased genesis. Consistently, certain phospholipids, such as miltefosine, that can disrupt the turnover of membranes, have antitumor activity. In the regard of the dependence of some specifics enzymes for the synthesis of membrane phospholipids, its inhibition constitutes an alternative of reduction of tumor development. Among the enzymes related to phospholipids turnover, there is the CTP: phosphoethanolamine cytidylyltransferase, which is usually overexpressed in tumor cells, included in lung cancer. Therefore, the therapeutic effect against cancer by pharmacological inhibition is expected. This study aim to evaluate the antineoplastic effects of CHY-1, a miltefosine analogue and potencial inhibitor of CTP: phosphoethanolamine cytidylyltransferase enzyme against non-small cell lung cancer. The analysis will be done by in vitro e in vivo assays, evaluating the activity over tumor cells and the immune system cells, and the response of these in the tumor. Others possible mechanisms will also be investigated. (AU)