Anti-migratory and cytotoxic effect of indole derivative in C6 glioma cells.

Gliomas are among the most common primary malignant brain tumors. Despite advances in cancer treatment, survival is very low, so the discovery of new therapeutic agents is essential. In this context, indole is an important source for the development of new bioactive molecules. A pharmacological screening of ten indole derivatives was carried out to evaluate the cytotoxic capacity against three tumor cell lines. After pharmacological screening, three compounds were selected, based on their high capacity to reduce cell proliferation, and their IC50 values were determined. Compound 9 exhibited the highest cytotoxic activity (IC50 = 0.4 µg/mL) in gliomas (C6 cell line), and were selected for further experiments. C6 cells were treated with compound 9 to evaluate cellular mechanisms such as colony formation and cell migration capacity and morphological alterations. Compound 9 decreased clone formation (0.4 and 0.8 µg/mL), and inhibited migration (0.2-0.8 µg/mL) in C6 cells. Morphological changes in cells treated with the compound 9 were also observed, such as chromatin condensation, and disorganization in cellular stress beams. Indole derivatives had a cytotoxic effect on tumor cells, and compound 9 showed the best anti-proliferative and anti-migratory activity in glioma cells.

Cytokines as an important player in the context of CAR-T cell therapy for cancer: Their role in tumor immunomodulation, manufacture, and clinical implications.

CAR-T cell therapies have been recognized as one of the most advanced and efficient strategies to treat patients with hematologic malignancies. However, similar results have not been observed for the treatment of solid tumors. One of the explanations is the fact that tumors have extremely hostile microenvironments for the infiltration and effector activity of T-cells, mainly due to the presence of highly suppressive cytokines, hypoxia, and reactive oxygen species. Taking advantage of cytokines functionally, new fourth-generation CAR constructs have been developed to target tumor cells and additionally release cytokines that can contribute to the cytotoxicity of T-cells. The manufacturing process, including the use of cytokines in the expansion and differentiation of T cells, is also discussed. Finally, the clinical aspects and the influence of cytokines on the clinical condition of patients, such as cytokine release syndrome, who receive treatment with CAR-T cells are addressed. Therefore, this review aims to highlight how important cytokines are as one of the major players of cell therapy.

Larvicidal formulation containing N-tosylindole: A viable alternative to chemical control of Aedes aegypti.

Aedes aegypti is currently a major public health problem. This mosquito is responsible for the spread of infectious diseases that have been causing epidemics worldwide. Surfactant-stabilized systems, such as microemulsions, liquid-crystalline precursors and liquid crystals, are promising sustained delivery formulations of hydrophilic and hydrophobic substances. These systems are biocompatible water-soluble reservoirs for N-tosylindole exhibiting biological activity against Aedes aegypti Linn. (Diptera: Culicidae) larvae. The ternary diagram displayed four regions: microemulsion (ME), liquid crystal (LC), emulsion (EM) and phase separation (PS). PLM and SAXS distinguished microemulsions, lamellar and hexagonal phase liquid crystals. The system had a lethal concentration of 50% (LC50 = 0.1 ppm, 0.36 µM) lower than pure N-tosylindole (0.24 ppm, 0.88 µM), which has limitations in aqueous media. Furthermore, the formulation displayed no toxicity to Artemia sp., a non-target organism. The system exhibited excellent larvicidal activity as an alternative to commercial larvicides that have shown resistance and toxicity to the environment by Ae. aegypti larvae due to prolonged use. In addition, a two-fold increase in potency was observed.