Highly Conformationally Restricted Cyclopropane Tethers with Three-Dimensional Structural Diversity Drastically Enhance the Cell Permeability of Cyclic Peptides.

The conformation of cyclic peptides is closely related to their physicochemical and biological properties, but their rational design to obtain a conformation with the desired properties is difficult. Herein, we present a new strategy by using conformationally restricted cyclopropane tethers (CPTs) to control the conformation and improve the cell permeability of cyclic peptides regardless of the amino acid sequence. Newly designed cis- or trans-CPTs with three-dimensional structural diversity were introduced into a model cyclic peptide, and the relationship between the conformation of the cyclic peptides and their cell permeability was analyzed.

Anti-plasticizing effect of amorphous indomethacin induced by specific intermolecular interactions with PVA copolymer.

The mechanism of how poly(vinyl alcohol-co-acrylic acid-co-methyl methacrylate) (PVA copolymer) stabilizes an amorphous drug was investigated. Solid dispersions of PVA copolymer, poly(vinyl pyrrolidone) (PVP), and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA) with indomethacin (IMC) were prepared. The glass transition temperature (Tg)-proportion profiles were evaluated by differential scanning calorimetry (DSC).

Development of a rapid and detailed structural identification system with an on-line immobilized enzyme reactor integrated into LC-NMR.

Immobilized enzyme reactors (IMERs) integrated into an LC-NMR system were developed for rapid and detailed structural identification of enzymatic reaction products. An on-column enzymatic reaction was achieved for immobilized cytochrome-c and dog microsomes. After the reaction, these products were analyzed by LC-NMR without any work-up processes.

Development of an automated synthesis system for preparation of glucuronides using a solid-phase extraction column loaded with microsomes.

An automated synthesis system using a solid-phase extraction (SPE) system and column packed with octadecylsilica (ODS), which was coated with phospholipid and loaded with dog liver microsomes, was developed for synthesis of glucuronides. Preparation of the microsome-immobilized SPE column, glucuronidation of drugs to synthesize the glucuronides and elution of the products were performed by an automated synthesis system. The phospholipid-coated SPE column and then the microsome-immobilized SPE column were readily prepared by allowing a solution containing L-alpha-dipalmitoylphosphatidylcholine to flow through the SPE column, and then by recycling a buffer solution containing dog liver microsomes through the resulting phospholipid-coated SPE column.

Novel dolabellane-type diterpene alkaloids with lipid metabolism promoting activities from the seeds of Nigella sativa.

[structure: see text] Four new dolabellane-type diterpene alkaloids, nigellamines A(1) (1), A(2) (2), B(1) (3), and B(2) (4), were isolated from the seeds of Nigella sativa. Their absolute stereostructures were determined on the basis of chemical and physicochemical evidence. Nigellamines A(1) (1), B(1) (3), and B(2) (4) were found to show potent lipid metabolism promoting activity in primary cultured mouse hepatocytes, and their activities were equivalent to that of a PPAR-alpha agonist, clofibrate.

Structures of new dammarane-type Triterpene Saponins from the flower buds of Panax notoginseng and hepatoprotective effects of principal Ginseng Saponins.

The saponin fraction from the flower buds of Panax notoginseng exhibited protective effect on liver injury induced by d-galactosamine and lipopolysaccharide. From the saponin fraction with hepatoprotective effect, five new dammarane-type triterpene saponins, notoginsenosides-O (1), -P (2), -Q (3), -S (4), and -T (5), were isolated together with nine known protopanaxadiol oligoglycosides. The structures of the new saponins were elucidated on the basis of chemical and physicochemical evidence.

Protective effects of polygodial and related compounds on ethanol-induced gastric mucosal lesions in rats: structural requirements and mode of action.

The methanolic extract from the leaves of Tasmannia lanceolata was found to potently inhibit ethanol-induced gastric lesions in rats. Through bioassay-guided separation, three known sesquiterpenes, polygodial, polygodial 12 alpha-acetal, and polygodial 12 beta-acetal, and a new sesquiterpene, methyl isodrimeninol, were isolated as the active constituents. Among them, polygodial showed very potent gastroprotective effects (ED(50)=0.