Bile salt hydrolysis is an important metabolic reaction in the bile salt metabolism of mammals. This reaction has a facilitating effect for bile salt excretion but can also be involved in various illnesses. In recent years interest has increased to use bile salt hydrolysis to influence the chole...

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in su...

Sodium hyodeoxycholate (NaHDC) is the main component of hog bile salts, which play a role in the absorption of sparingly soluble materials in the intestinal solution. The biosurfactant has an amphiphilic molecular structure, similar to that of ursodeoxycholate from bear gallbladder. Micelle form...

Colesevelam hydrochloride is a bile acid sequestrant used as a low density lipoprotein (LDL) reducing agent in hyperlipidemia with an additional advantage to improve glycemic control in type 2 diabetes patients. The objective of the study was to develop and validate a liquid chromatography tande...

Sphingosine kinases (SphKs) and their product sphingosine-1-phosphate (S1P) have been reported to regulate apoptosis and survival of liver cells. Cholestatic liver diseases are characterized by cytotoxic levels of bile salts inducing liver injury. It is unknown whether SphKs and/or S1P play a ro...

It has been previously reported that anions in common beverages may bind to bile acid sequestrants (BAS), reducing their capacity for binding bile acid salts. This study examined the ability of the novel BAS colesevelam hydrochloride (HCl), in vitro, to bind bile acid sodium salts following susp...

The iontophoretic delivery across rat skin of a quartemary ammonium salt (isopropamide: ISP), which is positively charged over a wide pH range, was measured in vitro. The study showed that: (a) iontophoresis significantly enhanced ISP delivery compared to passive transport; (b) ISP delivery was ...

A new method of determining the extraction constant (Ke, the true partition coefficient (TPC) and the formation constant (Kf) of ion-pairs, was developed by the solvent extraction technique. Ke and TPC were estimated from the reciprocals of the intercept and the slope of the regression line obta...

The effects of temperature, concentration, hydration, and sodium salicylate (SA) on the permeability of isopropamide iodide (ISP) through the excised abdominal mouse skin were investigated using the in vitro diffusion cell technique. The permeability of ISP was increased as the temperature of th...

Microbial production of (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one [(2S,3S)-DHMB], a key intermediate in the synthesis of diltiazem hydrochloride, was investigated. In the course of the screening of microorganisms for the hydrolysis of 3-acetoxy-2-(4-methoxyph...

Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from l- and d-threonine. As predicted in our previous paper (Tetrahedron Lett. 1995, 36, 8303–8306) all diastereomers of 2-iso-oxacephems can be prepared from the appropriate enantiomers of the amino acid threon...

The efficient synthesis of 3-, 4-, and 5-O-feruloylquinic acids starting from d-(−)-quinic acid is described. Esterification of suitably protected quinic acid derivatives with 3-(4-acetoxy-3-methoxyphenyl)-acryloyl chloride and subsequent hydrolysis of all the protecting groups afforded the titl...

trans-1-p-Methoxyphenyl-3-acetoxy-4-phenylazetidin-2-one (9) was obtained in high yield by changing the order of addition of the reagents in the acid chloride-imine cycloaddition of 5 and 6.

In this work, the structure of a novel 3-acetoxy-2-methyl-N-(4-methoxyphenyl) benzamide, was analyzed both experimentally and theoretically using three methods, X-ray single crystal diffraction technique, IR spectroscopy, and quantum chemical computation. The X-ray diffraction analysis indicates...

Several bovine spleen enzymes with acid pH optima, some of which hydrolyze bis(p-nitrophenyl)phosphate and therefore fit the definition of “phosphodiesterase IV,” were partially separated by isoelectric focusing and ion-exchange techniques. The activities were characterized by zymogram analysi...

Research on thymidylate synthase inhibitors has been a hot spot for anticancer drug development. Here, based on the structures and pharmacological properties of two types of TS inhibitors, through a molecular assembly principle of drugs design, we designed and synthesized a series of 30 novel ur...

A novel scaffold derived from l-SPD with a substituted thiophene group in the D ring were designed, synthesized, and evaluated for their binding affinities at dopamine (D1, D2 and D3) and serotonin (5-HT1A and 5-HT2A) receptors. Most of the tetracyclic compounds exhibited higher affinities for D...

Bi-acetylated l-stepholidine (l-SPD-A), a novel derivate of l-stepholidine (l-SPD), possesses a pharmacological profile of D1/5-HT1A agonism and D2 antagonism. In the present study, we examined the potential antipsychotic effect of l-SPD-A in a phencyclidine (PCP)-induced rat model of schizophre...

Several small molecules have been identified that induce glial cells to synthesize and secrete nerve growth factor (NGF), a critical neurotrophin that supports neuronal growth and survival, and as such show promise in the development of drugs for the chemoprevention of Alzheimer's disease. ...

ObjectiveTo compare the protein profile of culture supernatants in stimulated and unstimulated human fibroblasts to find some proteins indicating the presence of fibroblasts and their activation status.