1,2,3-Triazole tethered 2-mercaptobenzimidazole derivatives: design, synthesis and molecular assessment toward C6 glioma cell line.

Aim: Glioblastoma multiforme (GBM) is an aggressive cancer with very limited clinical therapies. Herein, we have designed novel mercaptobenzimidazole derivatives (1-7) as multitarget antineoplastic drugs and assessed their antiproliferative profiles on an experimental model for GBM, the C6 glioma line. Results: The target compounds were synthesized in few steps with reasonable yields (33-90%). Compounds 1 (∼18 µM) and 4 (∼20 µM) showed dose-dependent antiproliferative effects on C6 glioma and significantly increased early apoptosis, but only 4 disrupted the cell cycle progression and did not induce autophagy. Docking simulations suggested these compounds as dual kinase and colchicine binding site inhibitors. Conclusion: In spite of the limited selective toxicity, 4 hold the potential to be further optimized for the treatment of GBM.

Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells.

For more than 40 years, the fluid mosaic model of cellular membranes has supported our vision of an inert lipid bilayer containing membrane protein receptors that are randomly hit by extracellular molecules to trigger intracellular signaling events. However, the notion that compartmentalized cholesterol- and sphingomyelin-rich membrane microdomains (known as lipid rafts) spatially arrange receptors and effectors to promote kinetically favorable interactions necessary for the signal transduction sounds much more realistic. Despite their assumed importance for the dynamics of ligand-receptor interactions, lipid rafts and biomembranes as a whole remain less explored than the other classes of biomolecules because of the higher variability and complexity of their membrane phases, which rarely provide the detailed atomic-level structural data in X-ray crystallography assays necessary for molecular modeling studies. The fact that some alkylphospholipids (e.g. edelfosine: 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) selectively induce the apoptotic death of cancer cells by recruiting Fas death receptors and the downstream signaling molecules into clusters of lipid rafts suggests these potential drug targets deserve a more in-depth investigation. Herein, we review the structure of lipid rafts, their role in apoptotic signaling pathways and their potential role as drug targets for the treatment of cancer.

New insights into the chemistry and antioxidant activity of coumarins.

Coumarins are considered to be privileged structures due to their broad range of biological properties, including anticoagulant, anti-neurodegenerative, antioxidant, anticancer and antimicrobial activities. These interesting properties of coumarins can be ascribed to the chemical attributes of the 2H-chromen-2-one core; its aromatic ring can establish a series of hydrophobic, π-π, CH-π and cation-π interactions, and the two oxygen atoms in the lactone ring may hydrogen-bond to a series of amino acid residues in different classes of enzymes and receptors. Additionally, the double bond in the lactone helps to make the entire system planar, allows charge delocalization between the carbonyl group of the lactone and the aromatic ring and confers the characteristic fluorescence of this class of compounds, which can be explained by their preventing the trans-cis transformation of the double bond under ultraviolet (UV) irradiation. It is the possibility of radical delocalization in the 2H-chromen-2-one nucleus that makes most of the coumarins good antioxidants by acting as free radical scavengers, although some coumarins (mainly hydroxycoumarins) may also prevent the formation of free radicals by chelating metal ions. In this review, we provide a systematic analysis of the most important aspects surrounding the development of coumarins as antioxidants. Our analysis includes the synthesis of some complex antioxidant coumarins, strategies for structural modification to improve their antioxidant activities, qualitative/ quantitative structure-antioxidant relationships studies and the main in vitro assays used to evaluate their antioxidant properties.

Influence of essential oil fractionation by vacuum distillation on acaricidal activity against the cattle tick

The aim of this work was to study the influence of essential oil fractionation on acaricidal activity against the cattle tick Rhipicephalus (Boophilus) microplus. The citronella (Cymbopogon winterianus J.) and pepper tree (Schinus molle L.) essential oils were fractionated by vacuum distillation yielding fractions that were analyzed by the GC/MS. Laboratory tests were carried out to determine the effect of the total essential oil and fractions on larvae of the cattle tick R. (B.) microplus. The fractions 04 and 05 of the C. winterianus essential oil were the most active showing LC50 values of 1.20 and 1.34 μL/mL, respectively. The LC50 of the total oil was 3.30 μL/mL while the effect of the fractions 01, 02 and 03 was less pronounced, with LC50 values of 4.37, 4.24 and 3.49 μL/mL, respectively. The fraction 03 of the S. molle essential oil was the most active showing LC50 value of 8.80 μL/mL while the fractions 01 and 02 did not show toxic effects on the larvae.