Thiazolyl-isatin derivatives: Synthesis, in silico studies, in vitro biological profile against breast cancer cells, mRNA expression, P-gp modulation, and interactions of Akt2 and VIM proteins.

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC50 values of 1.23 and 1.39 µM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC50 values of 0.45 µM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7.

Evaluation of Antibacterial, Antineoplastic, and Immunomodulatory Activity of Paullinia cupana Seeds Crude Extract and Ethyl-Acetate Fraction.

Paullinia cupana (Guarana) is a native plant of Amazon region that has very traditional importance. Its seeds are rich in bioactive compounds, including tannins, which exhibit relevant properties. Objective. This study aimed to evaluate antibacterial, antineoplastic, and immunomodulatory activity of P. cupana seeds crude extract (CE) and ethyl-acetate fraction (EAF). Methods. Antibacterial activity was evaluated by determination of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Antineoplastic activity was evaluated by MTT assays in hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF-7), ductal carcinoma (T47-D), non-Hodgkin's B cell lymphoma (Toledo), T cell leukemia (Jukart), and Acute Leukemia (HL-60) cell lines. BALB/c mice splenocytes were treated to assess IFN-γ, IL-6, IL-17, and IL-10 levels by sandwich ELISA. Results. CE and EAF were not toxic to peripheral blood cells and splenocytes. CE and EAF fractions showed a bacteriostatic activity (MIC = 250 µg/mL) and presented IC50 values of 70.25 µg/mL and 61.18 µg/mL in HL-60 leukemia cell line. All cytokines evaluated had their levels reduced after treatment, following dose-response model. Discussion and Conclusion. Different biological activities were observed for both CE and EAF, suggesting P. cupana as a source of bioactive substances, especially tannins that may be used for several diseases treatments.