Convenient preparation of pinometostat and related 5′-deoxy-5′-amino adenosine derivatives as well as their activity against DOT1L

From adenosine and 2′-C-Me adenosine, a 3-step route towards nucleoside DOT1L inhibitors, including pinometostat, EPZ5677, and FED1, was established. With useful structural-activity relationship information, the newly prepared 2′-C-Me adenosine derivatives contribute to the limited repertoire of ribose-modified nucleoside DOT1L inhibitors. In general, this new synthetic method will facilitate not only the study of nucleoside DOT1L inhibitors, but also the synthetic and medicinal chemistry research of 5′-deoxy-5′-amino adenosine derivatives.     

Measurement of electrical charges carried by airborne bacteria laboratory-generated using a single-pass bubbling aerosolizer

Widely used bioaerosol generators like Collison nebulizer probably produce electrostatically charged particles, but the electrical charges carried by laboratory-generated airborne microorganisms using bubbling aerosolizers are poorly understood. In this study, we measured the fraction of neutral particles and number of elementary charges per particle as a function of the aerodynamic diameter of airborne bacteria (Escherichia coli and Enterococcus hirae). Bioaerosols were produced by a liquid sparging aerosolizer-type bubbling generator, with particle sizes ranging from roughly 0.6 to 2 μm. The experimental setup included an electrostatic precipitator and real-time devices including an electrometer, aerodynamic particle sizer, and electrical low-pressure impactor. Experimental results obtained for various operating conditions showed that aerosols produced with a higher bubbling airflow contained a larger proportion of neutral particles (from around 30% to 50%) and that bacteria carried a greater average absolute number of elementary charges (from around –10 to –60 elementary units) than those under lower airflow. Under the investigated conditions, a neutralization step is unnecessary because it may have a negative effect on the viability of sensitive microorganisms. Our results suggest that the neutral fraction can be used downstream of an electrostatic precipitator, and that this setup may have advantages over bipolar neutralizers.     

Four new prenylated flavonoids from the roots of Cudrania tricuspidata

Four new prenylated flavonoids, cudraflavanones E‐F (1–2) and cudraflavones F‐G (6–7), together with eight known compounds were isolated from the roots of Cudrania tricuspidata. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS and CD. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of thiourea derivatives as CCR4 antagonists

A series of thiourea derivatives have been synthesized. Their structures were confirmed by MS and 1H NMR. Several compounds showed potent activities as antagonists of CCR4 receptor.     

Characterization of biopartitioning micellar chromatography system using monolithic column by linear solvation energy relationship and application to predict blood–brain barrier penetration

The linear solvation energy relationship (LSER) was applied to characterize biopartitioning micellar chromatography (BMC) system using monolithic column, and was utilized to compare the above system with other physicochemical and biological processes in this study. The solute volume and HB basicity had the maximum influence on the retention of the solutes, and an increase in the dipolarity/polarizability, HB basicity, HB acidity or excess molar refraction of the solutes decreased the retention. Principal component analysis of LSER coefficients showed that the system had certain similarity to drug biomembrane transport processes, such as blood–brain barrier penetration, transdermal and oral absorption. The quantitative retention–activity relationship (QRAR) of drug penetration across blood–brain barrier was established and its predictive capability for this biological process was evaluated. With the aid of the high flow rate, the monolithic column significantly facilitated the high-throughput analysis of large compounds’ bank without changing the mechanism of the retention in BMC and without impairing good predictive capability of the biological processes. Accordingly, the BMC system, together with monolithic column, allows for high-throughput profiling the biological processes, such as blood–brain barrier penetration.     

Quantitative determination of β,β‐dimethylacrylshikonin (DASK) in rat whole blood by liquid chromatography–tandem mass spectrometry with pre‐column derivation and its pharmacokinetic application

A sensitive and selective liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method was developed and validated for the determination of β,β‐dimethylacrylshikonin (DASK) in rat whole blood. DASK was pretreated using pre‐column derivatization with 2‐mercaptoethanol followed by liquid–liquid extraction with cyclohexane. Detection was performed on Thermo Finnigan TSQ Quantum triple quadrupole mass spectrometer by selected reaction monitoring mode via electrospray ionization source. The linear range for the determination of DASK spiked in rat whole blood (0.25 mL) was 3–3000 ng/mL. The accuracy was within 9%. Intra‐ and inter‐day precisions were no more than 16.1 and 13.3%, respectively. The validated LC‐MS/MS method was successfully applied to the preliminary pharmacokinetic study in rats. After DASK administration (60 mg/kg, p.o.) in rats, pharmacokinetic parameters were obtained, where the area under the drug concentration–time curve was 2393.7 ± 224.4 ng h/mL and the elimination half‐life was 27.6 ± 5.3 h. Copyright © 2008 John Wiley & Sons, Ltd.     

A new triterpene saponin from the leaves of Ilex kudincha

A new compound,kudinoside LZ_2(1),was isolated from the leaves of Ilex kudincha.Its structure was elucidated by the combination of one- and two-dimensional NMR analysis,HR-ESI-MS,CD spectrum measurement and chemical evidences.     

Two New Alkaloids from Incarvillea sinensis

Two new alkaloids, incarvines E ( 1 ) and F ( 2 ), were isolated from the EtOH extract of the whole plant of Incarvillea sinensis. Their structures were elucidated by spectroscopic methods, including 1D‐ and 2D‐NMR.