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The combination of pharmacophoric nuclei with different targets has been a strategy for the development of new drugs aimed at improving cancer treatment. A series of ten novel phthalimido-thiazolidine-2-4-dione derivatives were synthesized by two different synthetic routes. The compounds were tested and evaluated in vitro, through antineoplastic activities against cancer cells. Cell cycle analysis and clonogenic assay were also performed. The synthesized FT-12 compound (9j) exhibited antiproliferative activity against Panc-1, Sk-mel-28, and PC-3 cells. FT-12 reduced the ability to form new clones, also caused irreversibility in cell cycle, inducing arrest in the S phase. Besides, the compound (FT-12) induced necrosis and apoptosis. The results suggest that phthalimido-thiazolidine derivatives may be useful in cancer therapy, highlighting compound FT-12 (9j) as a promising candidate. However, more studies must be carried out to confirm its viability.

The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia cell line (HL-60/MX1) by the MTT method. LPSF/NB-3 exhibited cytotoxicity in HL-60/MX1, but it was not toxic to healthy cells in the highest dose tested (100 μM). The protein extract of HL-60/MX1 cells treated with LPSF/NB-3 was subjected to proteomic analysis using two-dimensional chromatography coupled to mass spectrometry. We could identify a total of 2652 proteins, in which 633 were statistically modulated. Within the group of protein considered for the quantitative analysis with the established criteria, 262 were differentially expressed, 146 with increased expression and 116 with decreased expression in the sample treated with LPSF/NB-3 compared to the control. The following differentially expressed pathways were found: involving regulation of the cytoskeleton, DNA damage, and transduce cellular signals. Networks that were highlighted are related to the immune system. The ELISA technique was used to assess the immunomodulatory potential of LPSF/NB-3 in PBMCs. We observed significant decrease of IFNγ (p < 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways.

Glucocorticoids (GC) are widely used in the treatment of SSc, although there is not much evidence to prove the benefits offered by these drugs in this disease. In this study, we evaluated the effects of a GC on cytokine production in peripheral blood mononuclear cells (PBMC) of SSc patients. The effect of dexamethasone (DEX) was evaluated in PBMC of 21 SSc patients and 10 healthy volunteers after stimulation of cells with anti-CD3 and anti-CD28. Cytokines IL-2, IL-4, IL-6, IL-10, IL-17A, IL-17F, IFN-γ, TNF, and IL-1β were quantified in the culture supernatant by CBA or ELISA. Of the patients evaluated in this study, 8 (38%) were taking corticosteroids, and esophageal dysfunction was more frequent in these patients when compared to those who did not take corticosteroids. DEX (1.000 nM) treatment in PBMC of SSc patients stimulated with anti-CD3 and anti-CD28 promoted a significant reduction in IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-1β (p

The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p

To evaluate the effects of simvastatin in peripheral blood mononuclear cell (PBMC) cytokines profiles and correlate with the disease state of rheumatoid arthritis (RA) patients.The PBMC from 22 RA patients were purified and stimulated or not stimulated with phorbol myristate acetate/ionomycin and were treated with simvastatin in different doses. Cytokine levels were quantified by ELISA and patients were assessed for clinical and laboratory variables. This assessment included disease activity measures [Clinical Disease Activity Index (CDAI), Disease Activity Score for 28 joints (DAS28)] and a Health Assessment Questionnaire.The IL-17A, IL-6, IL-22 and IFN-γ were significantly reduced in a dose response after simvastatin treatment (50 μM, p = 0.0005; p 0.0001; p 0.02; p = 0.0005, respectively). The IL-17A and IL-6 cytokines were also significantly reduced in lower concentrations of simvastatin (10 μM) compared to controls (p = 0.018; p = 0.04) and compared to the standard drug (p = 0.007; p = 0.0001). The results also showed that only RA patients with severe disease (DAS285.1 and CDAI22) had poor response to simvastatin in reducing cytokines levels, mainly for IL-17A and IL-22 cytokines (p = 0.03; p = 0.039, respectively).The RA patients in clinical remission, mild or moderate had lower levels of all cytokines analyzed after simvastatin treatment, showing that these patients have better response to treatment. Our findings suggest that the simvastatin therapy modulates different cytokines in a dose dependent manner and its effect is associated with stratification of patients according to disease activity.