Difluoromethylborates and Muonium for the Study of Isonitrile Insertion Affording Phenanthridines via Imidoyl Radicals.

The 6-(difluoromethyl)phenanthridine unit is a highly attractive fluoroalkyl-substituted planar nitrogen heterocycle in pharmaceutical and agrochemical research. In this paper, we report that difluoromethylborates can be used as a source of difluoromethyl radicals for isonitrile insertion, leading to 6-(difluoromethyl)phenanthridines. Tuning the aryl substituents in the difluoromethylborates and oxidizing reagents enabled the synthesis of 6-(difluoromethyl)phenanthridines through the generation of difluoromethyl radical and spontaneous intramolecular cyclization of the CF2H-imidoyl radical intermediates. The presence of difluoromethyl radicals was experimentally confirmed, and the reaction mechanisms including imidoyl radical and prompt cyclization reactions could be supported theoretically. Furthermore, we obtained valuable information about the imidoyl radical intermediate by performing transverse-field muon spin rotation (TF-µSR) measurements of 2-isocyano-4'-methoxy-1,1'-biphenyl and using density functional theory (DFT) calculations to interpret the spectra. Muonium, a simple free radical, preferentially adds to the carbon atom of the isonitrile unit, yielding the corresponding imidoyl radical. The temperature dependence of the muon hyperfine coupling constant and the spin relaxation of the muoniated radical signal are compatible with the intramolecular cyclization of biaryl-substituted imidoyl radicals on the µs time scale.

Stereotaxic atlas of the goat brain for an accurate approach to the hypothalamic nuclei.

While the external acoustic meatus of mice, rats and cats are at right angles to the side of the head, they are angled forward in ruminants. Because of this, the coordinates of stereotaxic atlases created using the same methods as for small animals were not suitable for practical use and made it very difficult to place electrodes in hypothalamic nuclei. The aim of this study was to produce a highly accurate stereotaxic atlas for goats that enables precise placement of electrodes in the hypothalamic nuclei. A method of fixing the head in place so as to maintain the basis cranii interna in a horizontal position was established allowing right angled three dimensional axes to be superimposed in the brains of Japanese Saanen goats. This research attempted to establish a new landmark alternative to the external acoustic meatus. The new landmark is the extremitas posterior clivus presphenoidale (EPCP) at the base of cranial bone. This landmark can easily be visualized through lateral radiography. This enabled the AP (anterior-posterior) and H (height) coordinates of the position to be fixed at 30 and 5, respectively. The A30 and H5 coordinates of the serial frontal, sagittal, and horizontal stereotaxic atlases in the present experiment were set to coincide with the position of the EPCP. In order to clarify whether the deviation of the stereotaxic brain coordinates due to inconsistent immobilization the goat's head was eliminated, the AP and H coordinates of the extremitas anterior fossa hypophysialis and the extremitas posterior fossa hypophysialis were measured using the corrected axes. In the three dimensional stereotaxic atlas created using the new landmark, it became possible to approach the hypothalamic nuclei of goats accurately. This method significantly differentiates the stereotaxic atlas from its predecessors.

Growth inhibitory activities of crude extracts obtained from herbal plants in the Ryukyu Islands on several human colon carcinoma cell lines.

There is increasing interest in the use of herbs for the treatment of human diseases including cancer. Therefore, the purpose of this study was to determine whether crude extracts obtained from 44 herbal plants in the Ryukyu Islands might contain components capable of inhibiting the growth of a variety of human colon carcinoma cell lines. Leaves, roots and other parts of the plants were extracted with chloroform, and the crude extracts were dissolved in dimethylsulfoxide and used for the experiments. Extracts of Hemerocallis fulva, Ipomoea batatas, Curcuma longa, and Nasturium officinale caused marked dose-dependent growth inhibition, with IC(50) values in the range of 10-80 mug/ml. With the HCT116 cell line, the extracts of Hemerocallis fulva and Ipomoea batatas induced G1 cell cycle arrest after 48 h of treatment. In addition, we found that extracts of Curcuma longa, and Nasturium officinale induced apoptosis in these cells after 48 h of treatment. The present studies are the first systematic examination of the growth inhibitory effects of crude extracts obtained from herbal plants in the Ryukyu Islands. The findings provide evidence that several plants in the Ryukyu Islands contain components that may have anticancer activity.