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Metformin is a widely used drug in treating type 2 diabetes and insulin resistance and nowadays scientists are searching for new poten-tial and multiple roles in prevention and treatment of carcinogenic processes.The aim of the study was to compare the impact of normoglycemia and hyperglycemia with doses of metformin on vivacity and prolifer-ation of cancer cell lines (MCF-7, MCF-7/DX, A549, CCRF/CEM, THP-1, NHDF).We designed our experiment using raising glucose environment (40 mM, 100 mM, 150 mM, 300 mM) and we added increasing con-centrations of metformin (5 mM, 10 mM, 20 mM, 30 mM). We incubated cells for 24 h, 48 h, 72 h, 96 h. In order to measure of viabil-ity of cancer cells we use MTT assay - a typical test to mark cytotoxic effects of tested substances.Analysis indicated that populations of cancer cells in our terms was lowering, the incubation of 24 h and 48 h showed favorable results than 72 h and 96 h. In normoglycemic environment (glucose level about 100 mM) and after added metformin in various concentrations we observed decreasing percentage of vivid cells for all cancer cell lines (MCF-7, MCF-7/DX, A549, CCRF/CEM, THP-1).The results of our study showed beneficial effects of metformin on decreasing proliferation of cancer cells. Percentage of vivid popula-tions were lowering and we confirmed anti-cancer effect of this drug.Metformina jest lekiem szeroko stosowanym w leczeniu cukrzycy typu 2 i insulinooporności, a naukowcy koncentrują się obecnie na poszukiwaniu nowych możliwości i wielu ról w profilaktyce i leczeniu procesów nowotworowych.Porównanie wpływu normoglikemii i hiperglikemii z dawkami metforminy na żywotność i proliferację linii komórek nowotworowych (MCF-7, MCF-7/DX, A549, CCRF/CEM, THP-1, NHDF).Eksperyment wykonano z użyciem roztworów glukozy (o stężeniach 40 mM, 100 mM, 150 mM, 300 mM) i dodano rosnące stężenia metforminy (5 mM, 10 mM, 20 mM, 30 mM). Inkubowano komórki przez 24 godziny, 48 godzin, 72 godziny i 96 godzin. W celu pomiaru żywotności komórek nowotworowych wykorzystano test MTT – typowy test do oznaczania cytotoksycznego wpływu badanej substancji.Analiza wykazała, że populacje komórek nowotworowych uległy zmniejszeniu, inkubacja 24- i 48-godzinna wykazała korzystniejsze wyniki niż trwająca 72 h i 96 h. W środowisku normoglikemicznym (stężenie glukozy 100 mM), po dodaniu metforminy w różnych stężeniach zaobserwowano malejący odsetek żywych komórek wszystkich linii nowotworowych (MCF-7, MCF-7/DX, A549, CCRF/CEM, THP-1).Wyniki badania wykazały korzystny wpływ metforminy na zmniejszenie proliferacji użytych komórek nowotworowych. Odsetek ży-wych komórek w populacji zmniejszał się, potwierdzono również działanie antynowotworowe metforminy w eksperymencie.

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.

Neuroinflammation is considered to be one of the potential causes for the development of neurodegenerative diseases, including Alzheimer&rsquo, s disease. In this study, we evaluated the effect of four newly synthesized pyrrolo[3,4-d]pyridazinone derivatives on the neuron-like PC12 cells under simulated inflammation conditions by preincubation with lipopolysaccharide (LPS). Our novel derivatives are selective cyclooxygenase-2 (COX-2) inhibitors and have similar effects to nonsteroidal anti-inflammatory drugs (NSAIDs). We assessed viability (LDH assay), metabolic activity (MTT assay), DNA damage (number of double-strand breaks measured by fast halo assay), and the neuronal features of cells (average neurite length and neurite outgrowth measured spectrofluorimetrically). DCF-DA and Griess assays were also performed, which allowed determining the impact of the tested compounds on the level of oxygen free radicals and nitrites. LPS administration significantly negatively affected the results in all tests performed, and treatment with the tested derivatives in most cases significantly reduced this negative impact. Multiple-criteria decision analysis indicated that overall, the best results were observed for compounds 2a and 2b at a concentration of 10 &micro, M. The new derivatives showed intense activity against free oxygen radicals and nitrites. Reduced reactive oxygen species level also correlated with a decrease in the number of DNA damage. The compounds improved neuronal features, such as neurite length and outgrowth, and they also increased cell viability and mitochondrial activity. Our results suggest that derivatives 2a and 2b may also act additionally on mechanisms other than 3a and 3b.