Estudo do potencial quimioterápico de organocalcogenil-benzoatos em gliomas

Abstract

Glioblastoma is the most common and malignant of all cancers that affect the Central Nervous System, with a high rate of morbidity and mortality. Despite multimodal therapy with maximal surgical resection, followed by radiation and simultaneous use of chemotherapeutic agents, median survival is only 12 to 15 months after diagnosis. For this reason, the search for new substances that can give rise to more effective drugs is constant, and benzoates, organochalcogens and selenium derivatives are synthetic compounds that have been extensively researched, due to their pharmacological and biological properties, and promising previous results. Considering these facts, the objective of this work was to test the effects of benzoate derivatives containing an organoselenium group in their structure, in a glioblastoma lineage, specifically a C6 rat glioma lineage. Three organoclacogenyl-benzoate compounds were tested: 3-(phenylselanyl)prop-2-yn-1-yl nicotinate, 3-(phenylselanyl)prop-2-yn-1-yl benzoate, and 3-((4-fluorophenyl) benzoate)selenyl)prop-2-yn-1-yl, respectively called A, B and C, and treatment with dimethylsulfoxide vehicle was used as control. The strain was plated and treated with the compounds for different times (24, 48, 72h) and concentrations (1-100µM). After the treatments, tests such as the MTT test and counting the number of cells were performed. The compounds showed cytotoxic effects on the cell line tested, decreasing cell viability and the number of cells for all compounds. It was also verified the population doubling rate, the colony formation capacity, and the senescence induction potential by compound C, as it presented the most pronounced effects in the cytotoxicity tests. However, in these trials, there was no significant effect on any of the parameters analyzed. The results presented here are unprecedented and quite promising. As they are synthetic and unprecedented chemical structures, there are few comparative parameters about the activity and pharmacological potential of these compounds, but they have chemical and molecular characteristics, such as phenolic groups and the presence of selenium atoms, which indicate ease of passage through the blood-brain barrier. This property indicates a possible neurological effect, a mandatory prerequisite in chemotherapeutic agents aimed at brain cancers. Thus, this work introduces new compounds with antitumor potential, which can be better explored regarding the mechanism of action, antioxidant potential, among other characteristics in order to present themselves as possible adjuvants in the therapy for this tumor of such difficult treatment and such low survival.