Pharmacological Effects of Asiatic acid in Glioblastoma Cells under Hypoxia

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2hrs of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma

Characterization of polymer vector systems based on partially hydrolyzed polyoxazoline for gene transfection

In this work, partially hydrolyzed thermoresponsive polyoxazoline was used for complexation with DNA. The resulting polyelectrolyte complex particles were characterized by dynamic and electrophoretic light scattering. They showed narrow size distribution and hydrodynamic diameter of 183 +/- 5 nm at 65 degrees C. To improve stability of the system at physiological temperature, the particles were coated with cross-linked polymer shell on their surface. A cytotoxicity study indicated lower toxicity of the investigated systems compared to the referent polyethylenimine. In addition, the transfection ability of the resulting vector systems was evaluated by flow cytometry. Transfection efficiencies up to 65 % that of the referent polyethylenimine indicated the potential of the vectors for DNA delivery

Cytotoxic activity of a podophyllotoxin-like lignan from Linum tauricum Willd

The present study describes the preliminary evaluation of the cytotoxic activity of a podophyllotoxin-like compound 4’-demethyl-6-methoxypodophyllotoxin (4’-DM-6-Mptox), isolated as one of the main lignans of Linum tauricum Willd. ssp. tauricum. The cytotoxic effects 4’-DM-6-Mptox were assessed by the MTT-dye reduction assay against the human leukemic cell lines HL-60, BV-173 and LAMA-84. DNA-fragmentation analysis and NF-kB inhibition assay were performed in order to elucidate some of the mechanistic aspects of the cytotoxic action of the investigated compound. 4’-DM-6-Mptox was found to exert prominent cytotoxicity, with IC50 values being several-fold lower than those of the referent antineoplastic agent etoposide. The DNA-fragmentation analysis revealed that 4’-DM-6-Mptox treatment triggered apoptosis in BV-173 and HL-60 cells. In our hands 4’-DM-6-Mptox was found to induce concentration-dependent NF-kB inhibition in HeLa cells as assessed by the IL-6 luciferase gene reporter assay, which though not quite prominent, at least partly contributes to the cytotoxic potential of the tested lignan. On the basis of the results obtained it could be concluded that 4’-DM-6-Mptox necessitates further pharmacological and toxicological evaluation as a possible chemotherapeutic agent. Furthermore due to its relatively high concentrations in the described plant source the possibility for its use as a precursor for the semisynthetic production of lignan-based drugs, could be considered

Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety

A series of new hybrid molecules with a hydrazone fragment were synthesized and characterized by Fourier transform-infrared spectroscopy, nuclear magnetic resonance, mass spectrometry, and elemental analysis. The nuclear magnetic resonance spectra of the hydrazones 4a-c showed exchange of syn and antiperiplanar conformers around the amide bond, the more stable being the antiperiplanar one. The nuclear Overhauser effect spectroscopy (NOESY) spectra confirm E configuration around C=N bond. The tested compounds exhibited concentration-dependent cytotoxic effects against human tumor cell lines in a micromolar range (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay). Hydrazone 4a proved to be the most potent antiproliferative agent of the series. Within the antioxidant screening 8b exhibited the highest radical scavenging activity (% RSA max) and the largest rate constant for the reaction with 2,2-diphenyl-1-picrylhydrazyl

Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold

This study reports the synthesis of new 2H-chromene or coumarin based acylhydrazones, which were evaluated for their in vitro antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and compared to the first-line antituberculosis drugs, isoniazid (INH) and ethambutol (EMB). The most active compounds 7m (MIC 0.13 mu M), 7o (MIC 0.15 mu M) and 7k (MIC 0.17 mu M) demonstrated antimycobacterial activity at submicromolar concentration level and remarkably minimal associated cytotoxicity in the human embryonic kidney cell line HEK-293T. Structure-activity relationship for this class of compounds has been established