ao-128 and valiolamine

The number of people with diabetes is expected to rise from the current estimated 150 million to 220 million in 2010 and 300 million in 2025, and 90% is Type 2 diabetes or non-insulin dependent diabetes mellitus (NIDDM). Voglibose, one of the most important alpha-glucosidase inhibitors, delays the digestion and absorption of carbohydrates, thereby inhibiting postprandial hyperglycemia and hyperinsulinemia, and is the aid in the treatment of diabetes. In this paper, properties and the preparation of voglibose are reviewed.

Topics: Biochemistry; Carbohydrate Sequence; Cyclohexanols; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Inositol; Molecular Sequence Data

Hyper-pigmentation causes skin darkness and medical disorders, such as post-inflammatory melanoderma and melasma. Therefore, the development of anti-melanogenic agents is important for treating these conditions and for cosmetic production. In our previous paper, we demonstrated that the anti-diabetic drug voglibose, a valiolamine derivative, is a potent anti-melanogenic agent. In addition, we proposed an alternative screening strategy to identify valiolamine derivatives with high skin permeability that act as anti-melanogenic agents when applied topically. In this study, we synthesized several valiolamine derivatives with enhanced lipophilicity and examined their inhibitory effects in a human skin model. N-(2-hydroxycyclohexyl)valiolamine (HV) possesses a stronger inhibitory effect on melanin production than voglibose in a human skin model, suggesting that HV is a more potent anti-melanogenic agent for the skin.

Topics: Cells, Cultured; Cyclohexanols; Humans; Inositol; Melanins; Melanocytes; Monophenol Monooxygenase

Overproduction of melanin can lead to medical disorders such as postinflammatory melanoderma and melasma. Therefore, developing antimelanogenic agents is important for both medical and cosmetic purposes. In this report, we demonstrated for the first time that the antidiabetic drug voglibose is a potent antimelanogenic agent. Voglibose is a representative antidiabetic drug possessing inhibitory activity towards human α-glucosidase; it blocked the proper N-glycan modification of tyrosinase, resulting in a dramatic reduction of the tyrosinase protein level by altering its stability and subsequently decreasing melanin production. Acarbose, another antihyperglycaemic drug that has a lower inhibitory effect on human intracellular α-glucosidase compared with voglibose, did not cause any changes in either the N-glycan modification of tyrosinase or the tyrosinase protein level, indicating that voglibose was the most efficient antimelanogenic agent among the widely used antihyperglycaemic agents. Considering that voglibose was originally selected from the valiolamine derivatives in a screen for an oral antidiabetic drug with a strong inhibitory activity towards intestinal α-glucosidase and low cell permeability, we propose an alternative strategy for screening compounds from valiolamine derivatives that show high inhibitory activity towards human intracellular α-glucosidases and high cell permeability, with the goal of obtaining antimelanogenic agents that are effective inside the cells.

Topics: Acarbose; Cell Line, Tumor; Cell Proliferation; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Inflammation; Inositol; Mannosidases; Melanins; Melanocytes; Microscopy, Electron, Transmission; Monophenol Monooxygenase; Permeability; Polysaccharides; Real-Time Polymerase Chain Reaction; Skin

A rapid, low-cost, high sensitive and quantitative method to detect valiolamine in a medium for microbial culture, involving derivatization with a new labeling reagent, 4-methoxybenzenesulfonyl fluoride (MOBS-F), followed by reverse-phase high-performance liquid chromatography with ultraviolet (UV) detection with simple operation procedure. 4-Methoxybenzenesulfonyl chloride (MOBS-Cl) and 2-nitrobenzenesulfonyl chloride (NBS-Cl) were compared with MOBS-F as novel reagents in this paper, and the MOBS-F was chosen as the most suitable derivatization reagent. The column was thermostatic at 35 degrees C, the mobile phase flow-rate was 1.0mL/min and the detection wavelength was 240nm. For a biological sample, the separation of the derivatives was achieved using a gradient mobile system. The elution program is 88% phosphate buffer (50mM; pH=3.0) and 12% methanol for 23min, then 70% of phosphate buffer and 30% methanol for another 15min and finally 88% of phosphate buffer and 12% of methanol for 5min to re-equilibrate the column. The optimized conditions of the derivatization were as follows: derivatization reaction temperature 30 degrees C; derivatization reaction pH value 11.0, reaction time 10min and MOBS-F concentration higher than 1.5mg/mL for standard solutions and higher than 5.0mg/mL for the biological sample. Calibration curves were linear in the range of 0.050-25microg/mL for the standard solutions and 1.0-75microg/mL for the biological sample. The sensitive analytical method is helpful to control the biotechnological process of voglibose production and product quality control.

Topics: Biotechnology; Calibration; Chemistry Techniques, Analytical; Chromatography; Chromatography, High Pressure Liquid; Hydrogen-Ion Concentration; Inositol; Models, Chemical; Nitrobenzenes; Pharmaceutical Preparations; Quality Control; Temperature; Time Factors; Ultraviolet Rays

A new and stereoselective intramolecular direct aldol reaction of diketones derived from carbohydrates has been developed to construct carbocycles with D-gluco-, D-galacto-, D-manno-, and L-ido-configurations. The stereochemical outcome of the aldol reaction of the diketone is dependent on the base used. Transformation of D-gluco-aldols readily affords valiolamine which also constitutes a formal synthesis of voglibose. Facile conversion of D-gluco-cyclohexanones into validoxylamine G has been achieved in 12 steps with 15.1% overall yield from D-glucose.

Topics: Aldehydes; Carbohydrates; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Inositol; Ketones