Chemical structure of hydrolysates of cereulide and their time course profile.

Hydrolysates of an emetic toxin cereulide were found in the broth of Bacillus cereus. The ester cleaved depsipeptides of cereulide were synthesized using liquid phase fragment condensation method starting from commercially available amino acids. The chemical structure of hydrolysates was verified tetradepsipeptide l-O-Val-l-Val-D-O-Leu-d-Ala and dodecadepsipeptide (D-O-Leu-d-Ala-l-O-Val-l-Val)3 using LC-TOFMS. Quantitative analysis of cereulide in the broth revealed production of cereulide in the stationary phase and decomposition in the death phase. The increase in tetradepsipeptide continued after the stationary phase until decomposition occurred.

Cellular uptake evaluation of pentagamaboronon-0 (PGB-0) for boron neutron capture therapy (BNCT) against breast cancer cells.

Pentagamaboronon-0 (PGB-0), a curcumin analog compound, has been synthesized as a candidate of boron-carrier pharmaceutical (BCP) for boron neutron capture therapy (BNCT); however, this compound is poorly soluble in water. To improve its solubility, aqueous formulations of PGB-0 with a monosaccharide, fructose or sorbitol, were successfully synthesized, namely PGB-0-F and PGB-0-So, respectively. The cytotoxicity study showed that PGB-0-F and PGB-0-So exerted low cytotoxicity against MCF-7 and MDA-MB 231 breast cancer cells. The cellular uptake study using inductively coupled plasma optical emission spectrometry (ICP-OES) and DAHMI live-cell imaging indicated that these compounds were accumulated and distributed within the cytoplasm and cell nuclei. The cellular uptake mechanism was also evaluated to clarify the contribution of the glucose transporter, and the results demonstrated that these compounds entered through active transport into MCF-7 cells but through passive diffusion into MDA-MB 231 cells. In conclusion, the sugar formulations of PGB-0 only improved PGB-0 solubility but had no role in its cellular uptake.

Synthesis of the reported structure of homocereulide and its vacuolation assay.

Homocereulide, isolated from marine bacterium Bacillus cereus, is an analog of emetic toxin cereulide. There is no report on its structure determination and involvement in B. cereus-associated food poisoning. Homocereulide is a cyclic dodecadepsipeptide composed of l-O-Val-l-Val-d-O-Leu-d-Ala and l-O-allo-Ile-d-Val-d-O-Leu-d-Ala. Here, we synthesized homocereulide using liquid phase fragment condensation. The NMR spectrum of synthesized homocereulide confirmed the intended structure and LC-MS results were consistent with natural products. Morphological evaluation using HEp-2 cells showed higher toxicity with homocereulide (1.39 nM) than cereulide (3.95 nM). Though cereulide is the main component in broth culture, homocereulide is also likely involved in B. cereus-associated food poisoning.

Inhibition of influenza virus replication by adlay tea.

BACKGROUND: The present study was conducted aiming to examine the antiviral activity of adlay tea and its components against influenza viruses. We further aimed to clarify the mechanism by which these components regulate virus replication. RESULTS: Adlay tea at a concentration suitable for drinking inhibited the multiplication of influenza viruses. Moreover, our results suggest that individual components of the tea had antiviral activities against the influenza A/PR/8/34 virus. Adlay tea inhibited multiplication of the H1N1, H3N2 and B types of influenza virus, including oseltamivir-resistant viruses. In addition, adlay tea inhibited influenza infection during the periods of virus adsorption to the cell and virus replication. Adlay tea did not suppress hemagglutination inhibition or cell fusion, although it slightly inhibited virus binding to Malin Darby canine kidney cells. Furthermore, our findings suggest that the antiviral compounds included in adlay tea were ingredients other than polyphenols and that there were several types of effective compounds in adlay tea inhibiting several steps of viral replication. CONCLUSION: The results of the present study demonstrate that adlay tea had antiviral effects against influenza viruses. Our findings with respect to adlay tea suggest that the polyphenols might have a small influence on its antiviral activity and that other ingredients might have more influence. © 2017 Society of Chemical Industry.

Development and Elucidation of a Novel Fluorescent Boron-Sensor for the Analysis of Boronic Acid-Containing Compounds.

Novel boron-containing drugs have recently been suggested as a new class of pharmaceuticals. However, the majority of current boron-detection techniques require expensive facilities and/or tedious pretreatment methods. Thus, to develop a novel and convenient detection method for boron-based pharmaceuticals, imine-type boron-chelating-ligands were previously synthesized for use in a fluorescent sensor for boronic acid containing compounds. However, the fluorescence quantum yield of the imine-type sensor was particularly low, and the sensor was easily decomposed in aqueous media. Thus, in this paper, we report the development of a novel, convenient, and stable fluorescent boron-sensor based on O- and N-chelation (i.e., 2-(pyridine-2yl)phenol), and a corresponding method for the quantitative and qualitative detection of boronic acid-containing compounds using this commercially available sensor is presented.

Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy.

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

Use of a compact pixellated gamma camera for small animal pinhole SPECT imaging.

OBJECTIVES: Pinhole SPECT which permits in vivo high resolution 3D imaging of physiological functions in small animals facilitates objective assessment of pharmaceutical development and regenerative therapy in pre-clinical trials. For handiness and mobility, the miniature size of the SPECT system is useful. We developed a small animal SPECT system based on a compact high-resolution gamma camera fitted to a pinhole collimator and an object-rotating unit. This study was aimed at evaluating the basic performance of the detection system and the feasibility of small animal SPECT imaging. METHODS: The gamma camera consists of a 22 x 22 pixellated scintillator array of 1.8 mm x 1.8 mm x 5 mm NaI(Tl crystals with 0.2-mm gap between the crystals coupled to a 2" flat panel position-sensitive photomultiplier tube (Hamamatsu H8500) with 64 channels. The active imaging region of the camera was 43.8 mm x 43.8 mm. Data acquisition is controlled by a personal computer (Microsoft Windows) through the camera controller. Projection data over 360 degrees for SPECT images are obtained by synchronizing with the rotating unit. The knife-edge pinhole collimators made of tungsten are attached on the camera and have 0.5-mm and 1.0-mm apertures. The basic performance of the detection system was evaluated with 99mTc and 201Tl solutions. Energy resolution, system spatial resolution and linearity of count rate were measured. Rat myocardial perfusion SPECT scans were sequentially performed following intravenous injection of 201TlCl. Projection data were reconstructed using a previously validated pinhole 3D-OSEM method. RESULTS: The energy resolution at 140 keV was 14.8% using a point source. The system spatial resolutions were 2.8-mm FWHM and 2.5-mm FWHM for 99mTc and 201Tl line sources, respectively, at 30-mm source distance (magnification factor of 1.3) using a 1.0-mm pinhole. The linearity between the activity and count rate was good up to 10 kcps. In a rat study, the left ventricular walls were clearly visible in all scans. CONCLUSIONS: We developed a compact SPECT system using compact gamma camera for small animals and evaluated basic physical performances. The present system may be of use for quantitation of biological functions such as myocardial blood flow in small animals.

Long-term effect of motor cortical repetitive transcranial magnetic stimulation [correction].

Repetitive transcranial magnetic stimulation (rTMS) recently has been assessed as a noninvasive treatment modality for movement and psychiatric disorders, whereas the mechanism underlying the therapeutic effects is not fully understood. Studies in rodents showed lasting functional changes in some selected regions, such as limbic-associated structures, but unfocused brain stimulation did not clarify the regional effects. To address the topographical and temporal profiles of the effects on glucose metabolism in primate brain, we performed rTMS and repeated (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) before, during, and up to 16 days after rTMS in anesthetized cynomologous monkeys. We delivered a total of 2,000 pulses of 5 Hz-rTMS over the right precentral gyrus using a small-sized eight-figured coil that induced a localized electrical field. Voxel-based analysis in a standard space of the macaque brain showed statistically robust changes in FDG uptake: a decrease in the motor/premotor cortices and an increase in the limbic-associated areas involving the anterior/posterior cingulate, and orbitofrontal cortices. Interestingly, these uptake changes continued for at least 8 days and the magnitude of the lasting effects in the limbic-related areas was negatively correlated across subjects with those in the motor/premotor cortices. The results demonstrate that motor rTMS has a long-term lasting effect on motor-related regions and distant limbic-related areas via functional connections.