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Effect of the nitric oxide on anticancer activity of the thiosemicarbazone: 1-N-vanillin-4-N- (methyl)-thiosemicarbazone

Grant number: 20/16660-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2021
Effective date (End): May 31, 2023
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal researcher:José Clayston Melo Pereira
Grantee:Gian Vitor Rodrigues
Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Cancer is a disease, which caused around 12% of all human deaths worldwide each year. Thiosemicarbazones are compounds of interest in research related to the development of drugs in the fight against cancer. Among the most promising thiosemicarbazones, we highlight triapine, which showed excellent results in anticancer activity experiments in vitro. However, this thiosemicarbazone was investigated in more than 30 phases I and II clinical studies with results below expectations. Researchers have suggested that triapine can be inhibited during in vivo treatment due to the cyclo oxidation process forming its corresponding thiadiazole. Therefore, it was demonstrated that the thiadiazole derived from triapine does not show the antiproliferative activity of cancer cells, indicating that such a chemical process may be related to the low anticancer activity of the thiosemicarbazone in vivo experiments. Our group has shown that nitric oxide reacts with thiosemicarbazone in the presence of oxygen to form thiadiazoles. In our hypothesis, we believe that the cycle oxidation process of thiosemicarbazones, which could inhibit their anticancer activity, can occur through interaction with NO in the presence of oxygen in the biological system. Finally, in this project, our objective is to study the effect of nitric oxide on the in vitro antitumor activity of thiosemicarbazone.

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