New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

Objective: We aimed to detect novel in vitro effects of clopidogrel on platelets by assessment of the following parameters: malondialdehyde, glutathione, nitrite, aggregation response, and expressions of P-selectin, fibrinogen, apolipoprotein A1, apolipoprotein B, and phosphatidylserine.Materials and Methods: Platelets were obtained from healthy (n: 9) and hyperlipidemic (n: 9) volunteers. Expressions of P-selectin, fibrinogen, apolipoproteins A1/B and phosphatidylserine with and without clopidogrel were assayed by flow cytometry. Malondialdehyde, glutathione, aggregation and nitrite levels were also assayed. Results: Without clopidogrel, the baseline values of platelet aggregation, malondialdehyde, and expressions of P-selectin, fibrinogen and phosphatidylserine were significantly higher, whereas nitrite and expression of apolipoproteins A1/B were significantly lower in hyperlipidemics than in the healthy group. In both groups, clopidogrel significantly reduced aggregation and expression of fibrinogen, but it elevated nitrite levels. Clopidogrel significantly decreased P-selectin and phosphatidylserine expression and malondialdehyde but increased expressions of apolipoproteins A1/B only in hyperlipidemics. Conclusion: It seems that clopidogrel has some new in vitro antiplatelet effects. The present study is a basic in vitro study to suggest new insights into the effects of clopidogrel on platelet functions

Paradoxical role of humic acid in some of cancer cell lines

Mısırlı, Duygu (Arel Author) -- Conference: 41st FEBS Congress, Kusadası, Turkey, 3-8 September 2016.

Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells

In this study, a series of thiosemicarbazide derivatives 12-14, 1,2,4-triazol-3-thione derivatives 15-17 and compounds bearing 2-(4H-1,2,4-triazole-3-ylthio)acetamide structure 18-32 have been synthesized starting from phenolic compounds such as 2-naphthol, paracetamol and thymol. Structures and purity of the target compounds were confirmed by the use of their chromatographic and spectral data besides microanalysis. All of the synthesized new compounds 12-32 were evaluated for their anti-HIV activity. Among these compounds, three representatives 18, 19 and 25 were selected and evaluated by the National Cancer Institute (NCI) against the full panel of 60 human cancer cell lines derived from nine different cancer types. Antiproliferative effects of the selected compounds were demonstrated in human tumor cell lines K-562, A549 and PC-3. These compounds inhibited cell growth assessed by MTT assay. Compound 18, 19 and 25 exhibited anti-cancer activity with IC50 values of 5.96 μM (PC-3 cells), 7.90 μM (A549/ATCC cells) and 7.71 μM (K-562 cells), respectively. After the cell viability assay, caspase activation and Bcl-2 activity of the selected compounds were measured and the loss of mitochondrial membrane potential (MMP) was detected. Compounds 18, 19 and 25 showed a significant increase in caspase-3 activity in a dose-dependent manner. This was not observed for caspase-8 activity with compound 18 and 25, while compound 19 was significantly elevated only at the dose of 50 μM. In addition, all three compounds significantly decreased the mitochondrial membrane potential and expression of Bcl-2.publisher: Elsevier articletitle: Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2016.05.017 content_type: article copyright: © 2016 Elsevier Masson SAS. All rights reserved.status: publishe

Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents

A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamides 2a–e were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzene sulfonamides 1a–e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent