Microwave-accelerated energy-efficient esterification of free fatty acid with a heterogeneous catalyst

This paper shows energy-efficiency of microwave-accelerated esterification of free fatty acid with a heterogeneous catalyst by net microwave power measurement. In the reaction condition of 5 wt% sulfated zirconia and 1:20 M ratio of oil to methanol at 60°C and atmospheric pressure, more than 90% conversion of the esterification was achieved in 20 min by microwave heating, while it took about 130 min by conventional heating. Electric energy consumption for the microwave heating in this accelerated esterification was only 67% of estimated minimum heat energy demand because of significantly reduced reaction time.     

A novel potential therapeutic avenue for autism: design, synthesis and pharmacophore generation of SSRIs with dual action

Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT(1B/1D) autoreceptors antagonists motivated us to incorporate SSRIs and 5HT(1B/1D) antagonists in one 'hybrid' molecule. A library of virtual 'hybrid' molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (K(i)=0.013-5000 nM) and used as 3D query. Compounds with fit values (≥2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action.     

3,4-Disubstituted oxazolidin-2-ones as constrained ceramide analogs with anticancer activities

Heterocyclic analogs of ceramide as 3-alkanoyl or benzoyl-4-(1-hydroxy-2-enyl)-oxazolidin-2-ones were designed by binding of primary alcohol and amide in sphinogosine backbone as a carbamate. They were synthesized by addition of acyl halide to the common ring 4-(1-t-butyldimethylsilyloxyhexadec-2-enyl)-oxazolidin-2-one which was elaborated from chiral aziridine-2-carboxylate including stereoselective reduction and ring opening reactions as key steps. Other analogs with different carbon frame at C4 position which is corresponding to the sphingoid backbone were prepared from 3-cyclopentanecarbonyl-4-(1-t-butyldimethylsilyloxybut-2-enyl)-oxazolidin-2-one and straight and cyclic alkenes by cross metathesis. All compounds were tested as antileukemic drugs against human leukemia HL-60 cells. Many of them including propionyl, cyclopentanoyl and p-nitrobenzoyl-4-(1-hydroxyhexadec-2-enyl)-oxazolidin-2-ones showed better antileukemic activities than natural C2-ceramide with good correlation between cell death and DNA fragmentation. There is a drastic change of the activities by the carbon chain lengths at C4 position. Cytotoxicity was induced by caspase activation without significant accumulation of endogenous ceramide concentration or any perturbation of ceramide metabolism.     

Environmental epigenetics in metal exposure

Although it is widely accepted that chronic exposure to arsenite, nickel, chromium and cadmium increases cancer incidence in individuals, the molecular mechanisms underlying their ability to transform cells remain largely unknown. Carcinogenic metals are typically weak mutagens, suggesting that genetic-based mechanisms may not be primarily responsible for metal-induced carcinogenesis. Growing evidence shows that environmental metal exposure involves changes in epigenetic marks, which may lead to a possible link between heritable changes in gene expression and disease susceptibility and development. Here, we review recent advances in the understanding of metal exposure affecting epigenetic marks and discuss establishment of heritable gene expression in metal-induced carcinogenesis.Key words: environmental metal, epigenetic, metal carcinogenesis, histone modification, DNA methylation, chromatin, gene expression     

One step forward: the use of transgenic zebrafish tumor model in drug screens

The zebrafish (Danio rerio) has been an experimental model in the developmental biology and toxicology since the 1950s. In recent years, with the aid of transgenic technology, it has also gained an increasing popularity to model human diseases, including various cancers. As a feasible vertebrate model for large-scale chemical screens, the zebrafish has also given us a new option for the search of potential anticancer drugs. It is hopeful that in the near future with automation and analytical tools, drug development processes will be significantly shortened for quick and effective identification of candidate drugs.     

Ultrahigh-resolution optical trap with single-fluorophore sensitivity

We present a single-molecule instrument that combines a time-shared ultrahigh-resolution dual optical trap interlaced with a confocal fluorescence microscope. In a demonstration experiment, we observed individual single fluorophore-labeled DNA oligonucleotides to bind and unbind complementary DNA suspended between two trapped beads. Simultaneous with the single-fluorophore detection, we clearly observed coincident angstrom-scale changes in tether extension. Fluorescence readout allowed us to determine the duplex melting rate as a function of force. The new instrument will enable the simultaneous measurement of angstrom-scale mechanical motion of individual DNA-binding proteins (for example, single-base-pair stepping of DNA translocases) along with the detection of properties of fluorescently labeled protein (for example, internal configuration).