trans-2-Pentenal, an Active Compound in Cigarette Smoke, Identified via Its Ability to Form Adducts with Glutathione.
In this study, we searched for novel α,β-unsaturated carbonyl compounds other than ACR, CA, and MVK. We selected candidate compounds in CSE based on accurate mass values generated using LC/MS analysis of products formed between CSE and GSH, and identified these using GC/MS analysis and library screening. As a result, we isolated trans-2-methyl-2-butenal, 2-methyl-2-cyclopenten-1-one, 3-methyl-2-cyclopenten-1-one, and furfural, which were poorly reactive with GSH and only very weakly inhibited growth of Colon-26 mouse carcinoma cells and BALB/3T3 clone A31 mouse normal cells. We also isolated 2-cyclopenten-1-one,...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Hatai M, Horiyama S, Yoshikawa N, Kinoshita E, Kagota S, Shinozuka K, Nakamura K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Structural Optimization of Caffeoyl Salicylate Scaffold as NO Production Inhibitors.
Abstract Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxid...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Yu P, Xia CJ, Li DD, Wang Z, Xiao W, Zhao LG Tags: Chem Pharm Bull (Tokyo) Source Type: research

Thiocyanation of Aromatic and Heteroaromatic Compounds with 1-Chloro-1,2-benziodoxol-3-(1H)-one and (Trimethylsilyl)isothiocyanate.
Abstract Thiocyanation of aromatic compounds has been investigated using the combination of 1-chloro-1,2-benziodoxol-3-(1H)-one (1) and (trimethylsilyl)isothiocyanate (TMSNCS). The reaction with electron rich aromatic compounds proceeded smoothly to provide the thiocyanated products in high yield, while electron deficient heteroaromatic compounds were not suitable for this reaction. In these reactions, the regioselectivity was generally high. Transformations of the products were also investigated to demonstrate the utility of the reaction. Based on NMR experiments, we propose that thiocyanogen chloride is generate...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Ito Y, Touyama A, Uku M, Egami H, Hamashima Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

2,2'-Biphenol/B(OH)3 Catalyst System for Nazarov Cyclization.
Abstract A novel catalyst system-a combination of the readily available 2,2'-biphenol with the inexpensive, nontoxic, and eco-friendly B(OH)3-promoted the Nazarov cyclization of activated and inactivated divinyl ketones to afford the corresponding cyclopentenones up to 96% yield under, in a cis-selective manner. Compared with the conventional harsh conditions with hazardous reagents, user-friendly method was established with bench-stable and easy-to-handle reagents. PMID: 31474725 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Sugimoto K, Oshiro M, Hada R, Matsuya Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics.
Abstract The word "theranostics," a portmanteau word made by combining "therapeutics" and "diagnostics," refers to a personalized medicine concept. Recently, the word, "radiotheranostics," has also been used in nuclear medicine as a term that refer to the use of radioisotopes for combined imaging and therapy. For radiotheranostics, a diagnostic probe and a corresponding therapeutic probe can be prepared by introducing diagnostic and therapeutic radioisotopes into the same precursor. These diagnostic and therapeutic probes can be designed to show equivalent pharmacokinetics, ...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Ogawa K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Foreword.
PMID: 31474727 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Moribe K, Yonemochi E Tags: Chem Pharm Bull (Tokyo) Source Type: research

Intermolecular Interactions between Drugs and Aminoalkyl Methacrylate Copolymer in Solution to Enhance the Concentration of Poorly Water-Soluble Drugs.
Abstract An aminoalkyl methacrylate copolymer, Eudragit® E (EUD-E), has gained tremendous attention as a solid dispersion carrier because it efficiently stabilizes drugs in the amorphous state. Furthermore, EUD-E remarkably enhances drug dissolution in water. This review focuses on the interaction between drugs and EUD-E in solution, which contributes to the enhancement of drug concentration. Studies examining interactions between acidic drugs and EUD-E in organic solvents have revealed that the interaction occurs predominantly by electrostatic interaction, including hydrogen bonding and dipolar interactions. ...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Higashi K, Ueda K, Moribe K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Modification of Drug Crystallization by Cyclodextrins in Pre-formulation Study.
Abstract Controlling drug crystallization is one of the important issues in pre-formulation study. In recent years, advanced approaches including the use of tailor-made additives have gathered considerable attention to control crystallization behavior of drugs. This review focuses on the use of hydrophilic cyclodextrins (CDs) as additives for controlling drug crystallization. CDs affect the crystallization of drugs in solution and in solid state based on a host-guest interaction. For example, 2,6-di-O-methyl-β-CD and 2-hydroxybutyl-β-CD suppressed solution-mediated transition of drugs during crystallizat...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Iohara D, Anraku M, Uekama K, Hirayama F Tags: Chem Pharm Bull (Tokyo) Source Type: research

Preparation of Amorphous Composite Particles of Drugs with Ursodeoxycholic Acid as Preclinical Formulations.
Abstract We studied the possibility of using ursodeoxycholic acid (UDCA) as an excipient to create an amorphous composite that can be administered to animals in preclinical studies of experimental drugs. Three UDCA-based amorphous samples composed of nifedipine (NIF), indomethacin (IND), and naproxen (NAP) were found by screening. The UDCA-based formulations were adjudged amorphous by solid-state analysis using X-ray powder diffraction and differential scanning calorimetry. In addition, amorphous samples of NIF-UDCA, IND-UDCA, and NAP-UDCA did not crystallize while in 1% methyl cellulose (MC) solution for 120&thin...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Tanida S, Yoshimoto A, Yoshida M, Uchiyama H, Kadota K, Tozuka Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Measurement of the Water Content in Semi-solid Formulations Used to Treat Pressure Ulcers and Evaluation of Their Water Absorption Characteristics.
Abstract We investigated the water contents in commercial semi-solid preparations used for pressure ulcer (PU) treatment using near-IR spectroscopy (NIRS) and compared the results with those measured using the Karl Fischer (KF) method. The aim of this study was to determine a standard method and select the appropriate topical preparation with the optimal moisture for PU treatment. The water absorption properties of bases and formulations were evaluated with a time-dependent factor using Transwell as the model membrane. KF and NIRS were applicable as measurement methods of the water content in semi-solid formulatio...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Hoshino T, Azuma M, Yamada Y, Titapiwatanakun V, Yoshimura Fujii M, Yamamoto Y, Koide T, Fukami T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Crystal Structures of Flavone C-Glycosides from Oolong Tea Leaves: Chafuroside A Dihydrate and Chafuroside B Monohydrate.
Abstract Chafuroside A and chafuroside B are flavone C-glycosides isolated from oolong tea leaves. They have a number of beneficial pharmacological activities related to antiinflammation at various concentrations. However, no crystallographic study of chafurosides has yet been reported. In the present study, the crystal structures of chafuroside A and chafuroside B were investigated using single-crystal X-ray diffraction. The asymmetric unit of the chafuroside A crystal consists of one chafuroside A and two water molecules, and that of chafuroside B contains one chafuroside B and one water molecule. The flavone mo...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Iwao Y, Ishida H, Kimura SI, Wakimoto T, Kondo H, Itai S, Noguchi S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Improving the Solid-State Photostability of Furosemide by Its Cocrystal Formation.
Abstract The photostability of three types of furosemide (FUR) cocrystal (FUR-caffeine, FUR-urea, and FUR-nicotinamide cocrystals) was studied under irradiation with a D65 fluorescent lamp. The coloration of the FUR-urea pellets was significantly faster than that of the intact FUR, whereas the coloration of FUR-nicotinamide was suppressed compared with that of intact FUR and the other cocrystals. In the case of FUR-urea, the chemical degradation of FUR increased by approximately 6.6% after irradiation for 90 d. On the other hand, FUR-nicotinamide showed better chemical stability, with only 1.3% of FUR degra...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Teraoka R, Fukami T, Furuishi T, Nagase H, Ueda H, Tode C, Yutani R, Kitagawa S, Sakane T Tags: Chem Pharm Bull (Tokyo) Source Type: research

A New Method for Classification of Salts and Cocrystals Using Solid-State UV Spectrophotometry.
Abstract Salt and cocrystal formulations are widely used as techniques to improve physicochemical properties of compounds. Some spectrometric techniques to distinguish cocrystals from salts have been reported; however, it has not been possible to adapt these formulations with many compounds, because of limitations, high difficulty, and exceptions. Therefore, we focused on the possibility of UV spectrometry, which had not been reported as a classification technique for salts and cocrystals. The integration values of solid-state UV/visible (Vis) spectra of indomethacin salts were larger than those of physical mixtur...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Kiguchiya A, Teraoka R, Sakane T, Yonemochi E Tags: Chem Pharm Bull (Tokyo) Source Type: research

Asymmetric Total Syntheses and Structure Elucidations of (+)-Eurotiumide F and (+)-Eurotiumide G.
Abstract Asymmetric total syntheses of dihydropyran containing natural products, (+)-eurotiumide F and (+)-eurotiumide G have been described. These total syntheses revealed the absolute configuration of eurotiumide F and G, and confirmed the reported structure of eurotiumide F and revised the reported structure of eurotiumide G. Highlight of these syntheses is thermal rearrangement with 4-methoxyisochroman-1-one derivative having propargyl ether on phenolic ether under thermal condition to construct dihydropyran ring. X-Ray crystallographic analysis of (+)-eurotiumide G clarified the stereochemistry at the C1-posi...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Nakayama A, Sato H, Nagano S, Karanjit S, Imagawa H, Namba K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Computational Study on the Assembly of Amyloid β-Peptides in the Hydrophobic Environment.
Computational Study on the Assembly of Amyloid β-Peptides in the Hydrophobic Environment. Chem Pharm Bull (Tokyo). 2019;67(9):959-965 Authors: Qu L, Fudo S, Matsuzaki K, Hoshino T Abstract Fibrillated aggregation of amyloid β (Aβ) peptides is a potential factor causing toxic amyloid deposition in neurodegenerative diseases. A toxic fibril formation of Aβ is known to be enhanced on the ganglioside-rich lipid membrane containing some amounts of cholesterol and sphingomyelin. This ganglioside-rich membrane is supposed to provide a hydrophobic environment that promotes the formation of...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Qu L, Fudo S, Matsuzaki K, Hoshino T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Amphiphilic Endomorphin-1 Derivative Functions as Self-assembling Nanomedicine for Effective Brain Delivery.
In this study, we develop a short-peptide self-delivery system for brain targets with the capability to deliver EM-1 without vehicle. Two amphiphilic EM-1 derivatives, C18-SS-EM1 and C18-CONH-EM1, were synthesized by attaching a stearyl moiety to EM-1 via a disulfide and amide bond, respectively. The amphiphilicity of EM-1 derivatives enabled self-assembling into nanoparticles for brain delivery. The study assessed morphology, circular dichroism, and metabolic stability of the formulations, as well as their pharmacodynamics and in vivo distribution, directly monitored by near-IR fluorescence imaging in mouse brains. In aqu...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Liu H, Zhao X, Liang S, Fan L, Li Z, Zhang Y, Ni J Tags: Chem Pharm Bull (Tokyo) Source Type: research

Fabrication of Zero-Order Sustained-Release Floating Tablets via Fused Depositing Modeling 3D Printer.
In this study, zero-order sustained-release floating tablet was fabricated using FDM 3D printer. Filaments comprising poorly water-soluble weak base drug, itraconazole (ITZ) and polymers (hydroxypropyl cellulose and polyvinylpyrrolidone) were prepared, and tablets with a hollow structure and different outside shell thicknesses were fabricated. In the 3D printed tablets, ITZ existed as an amorphous state and its solubility improved markedly. As the outside shell thickness of the tablet increased, drug release was delayed and floating time was prolonged. In the tablets with 0.5 mm of the upper and bottom layer thickne...
Source: Chemical and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Kimura SI, Ishikawa T, Iwao Y, Itai S, Kondo H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Synthesis, structure activity relationship and anti-influenza A virus evaluation of oleanolic acid-linear amino derivatives.
Abstract Oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor in our earlier studies. In the present work, 20 compounds were prepared by structural modifications of OA, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in MDCK cells were evaluated. Based on the biological result, structure-activity relationship (SAR) was discussed. Compound 10 with six-carbon chain and a terminal hydroxyl group showed the strongest anti-influenza activity with an IC50 of 2.98 μM, which is an order of magnitude more potent than OA. Hemagglutination inhibition and Surface plasmo...
Source: Chemical and Pharmaceutical Bulletin - August 22, 2019 Category: Drugs & Pharmacology Authors: Li W, Yang F, Meng L, Sun J, Su Y, Shao L, Zhou D, Yu F Tags: Chem Pharm Bull (Tokyo) Source Type: research

Significance of data selection in deep learning for reliable binding mode prediction of ligands in the active site of CYP3A4.
Abstract For rational drug design, it is essential to predict the binding mode of protein-ligand complexes. Although various machine learning-based models have been reported that use convolutional neural networks (deep learning) to predict binding modes from three-dimensional structures, there are few detailed reports on how best to construct and use datasets. Here, we examined how different datasets affected the prediction of the binding mode of CYP3A4 by a three-dimensional neural network when the number of crystal structures for the target protein was limited. We used four different training datasets: one large...
Source: Chemical and Pharmaceutical Bulletin - August 17, 2019 Category: Drugs & Pharmacology Authors: Sato A, Tanimura N, Honma T, Konagaya A Tags: Chem Pharm Bull (Tokyo) Source Type: research

An improved protocol for the virtual screening discovery of novel histone deacetylase inhibitors.
Abstract Histone deacetylases (HDACs) are enzymes that play a key role in structural modification and gene expression. The overexpression of HDAC is associated with cancer, and thus inhibiting the enzyme could be an efficient cancer therapy. To discover new HDAC inhibitors (HDACis), we proposed an improved protocol combining a hierarchical pharmacophore search, molecular docking, and molecular dynamic simulations. The test results showed that the improved screening protocol effectively reduced the false-positive rates of drug-like chemicals. Based on the protocol, we obtained 16 hit compounds as potential HDACis f...
Source: Chemical and Pharmaceutical Bulletin - August 9, 2019 Category: Drugs & Pharmacology Authors: Song Q, Liu T, Liu Y, Wang S, Fan C, Zheng L, Bao Y, Sun L, Yu C, Sun Y, Song Z, Wang G, Huang Y, Li Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Transporter-Targeted Bile Acid-Camptothecin Conjugate for Improved Oral Absorption.
Abstract Camptothecin (CPT), a natural alkaloid, possesses potent anticancer activity. However, its application was terminated due to its low bioavailability and high toxicity. This work evaluated the potential of deoxycholic acid-CPT conjugate (G2) to improve the oral absorption of CPT. Deoxycholic acid significantly reduced cytotoxicity and inhibited the uptake of G2, in vitro. And G2 showed sodium-dependent uptake. In addition, in vivo study in rats indicated that the oral bioavailability of G2 was 2.06-fold higher than that of CPT. The present study suggested that using bile acid as the conjugated moiety is a ...
Source: Chemical and Pharmaceutical Bulletin - August 6, 2019 Category: Drugs & Pharmacology Authors: Xiao L, Zhou Y, Zhang X, Ding Y, Li Q Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development of Metal Nanoparticle Catalysis toward Drug Discovery.
Abstract Transition-metal nanoparticles (NPs) catalysts supported on solid material represent one of the most important subjects in organic synthesis due to their reliable carbon-carbon or carbon-heteroatom bond-forming cross-coupling reactions. Therefore methodologically and conceptually novel immobilization methods for nonprecious transition-metal NPs are currently required for the development of organic, inorganic, green, materials, and medicinal chemistry. We discovered a self-assembled Au-supported Pd NPs catalyst (SAPd(0)) and applied it as a catalyst to Suzuki-Miyaura coupling, Buchwald-Hartwig reaction, Ca...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Arisawa M Tags: Chem Pharm Bull (Tokyo) Source Type: research

Beijinchromes A-D, Novel Aromatic Compounds Isolated from Nocardia beijingensis NBRC 16342.
Abstract Nocardia is a potent bacterial producer of bioactive compounds. From a culture of Nocardia beijingensis NBRC 16342, we isolated four aromatic compounds, named beijinchromes A-D (1-4). We purified them by silica gel chromatography and reverse phase HPLC, and identified their structures by NMR and high resolution (HR)-MS analyses. 1, 2, and 4 are novel 1,2,3,8-tetrasubstituted naphthalenes, and 3 is a novel 3,8-disubstituted ortho-naphthoquinone. 1 and 2 exert antioxidant activities, and 3 exhibits antibiotic activity. Remarkably, the putative biosynthetic gene clusters for 1-4 are widely distributed in 37 ...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Hoshino S, Awakawa T, Zhang H, Hayashi F, Abe I Tags: Chem Pharm Bull (Tokyo) Source Type: research

Novel Compound-Target Interactions Prediction for the Herbal Formula Hua-Yu-Qiang-Shen-Tong-Bi-Fang.
In this study, we predicted the targets of the compounds from the TBF formula via network analysis and in silico computing. Initially, the information of the phytochemicals contained in the plants of the herbal formula was collected, and subsequently computed to their corresponding fingerprints for the sake of structural similarity calculation. Then a compound structural similarity network infused with available target information was constructed. Five local similarity indices were used and compared for their performance on predicting the potential new targets of the compounds. Finally, the Preferential Attachment Index wa...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Wang Z, Lin HH, Linghu K, Huang RY, Li G, Zuo H, Yu H, Chan G, Hu Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development and Evaluation of a Water-in-oil Microemulsion Formulation for the Transdermal Drug Delivery of Teriflunomide (A771726).
Abstract Teriflunomide (TEF, A771726) is the active metabolite of leflunomide (LEF), a disease-modifying anti-rheumatic drug. The main purpose of this study was to develop and evaluate water-in-oil (W/O) microemulsion formulation of TEF. The W/O microemulsion was optimized formula is the physical and chemical stability of lecithin, ethanol, isopropyl myristate (IPM) and water (20.65/20.78/41.52/17.05 w/w) by using the pseudo-ternary phase diagram and the average droplet size is about 40 nm. The permeability of TEF microemulsion is about 6 times higher than control group in vitro penetration test. The...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Cao Y, Gao H, Xia H, Zhu X, Li B, Zhou X, Jin Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Analysis of Microstructure of Granules Prepared by Continuous Twin Screw Granulator Using X-Ray Micro-computed Tomography.
This study revealed that the drug dissolution rate was regulated by a disintegration step in which the porosity of granules plays an important role. PMID: 31366829 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Matsui Y, Ando Y, Yamamoto K, Watano S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Effect of Drug Combination on Omeprazole Metabolism by Cytochrome P450 2C19 in Helicobacter pylori Eradication Therapy.
Abstract Helicobacter pylori (H. pylori) infection is common and can result in gastric and duodenal ulcers, and in some cases, gastric lymphoma and cancer. Omeprazole (OMP)-in combination with clarithromycin (CLR), amoxicillin (AMX), tinidazole (TND), or metronidazole (MET)-is used in double or triple combination therapy for eradication of H. pylori. However, the roles of the drugs other than OMP are not clearly understood. Therefore, in the present study, we aimed to investigate any effects of these drugs on OMP metabolism by wild-type CYP2C19 using spectroscopy and enzyme kinetics. The dissociation constants (Kd...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Attia TZ, Yamashita T, Tsujino H, Derayea SM, Tsutsumi Y, Uno T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Designing of Stable Co-crystals of Zoledronic Acid Using Suitable Coformers.
In this study the coformers selected were DL-tartaric acid and nicotinamide based on ease of hydrogen bond formation. The co-crystal of zoledronic acid with DL-tartaric acid were prepared in three ratios (1 : 1, 1 : 2 and 2 : 1) by slow solvent evaporation method and with nicotinamide in 1 : 1 ratio by dry grinding method. The formation of co-crystal was confirmed by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier transform (FT)IR. The dynamic solubility of co-crystals with DL-tartaric acid in the ratios 1 : 1, 1&t...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Varma A, Laxmi P, Pai A, Pai G, Sg V, Badamane Sathyanarayana M Tags: Chem Pharm Bull (Tokyo) Source Type: research

Discovery and Biological Evaluation of Potent and Orally Active Human 11 β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors for the Treatment of Type 2 Diabetes Mellitus.
Discovery and Biological Evaluation of Potent and Orally Active Human 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors for the Treatment of Type 2 Diabetes Mellitus. Chem Pharm Bull (Tokyo). 2019;67(8):824-838 Authors: Koike T, Shiraki R, Sasuga D, Hosaka M, Kawano T, Fukudome H, Kurosawa K, Moritomo A, Mimasu S, Ishii H, Yoshimura S Abstract We synthesized and evaluated novel 5-[2-(thiophen-2-yl)propan-2-yl]-4H-1,2,4-triazole derivatives as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors. Optimization of the thiophene ring and the substituents on the 1,2,4-triazole ring...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Koike T, Shiraki R, Sasuga D, Hosaka M, Kawano T, Fukudome H, Kurosawa K, Moritomo A, Mimasu S, Ishii H, Yoshimura S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Qualitative and Quantitative Analysis of the Saponins in Panacis Japonici Rhizoma Using Ultra-Fast Liquid Chromatography Coupled with Triple Quadrupole-Time of Flight Tandem Mass Spectrometry and Ultra-Fast Liquid Chromatography Coupled with Triple Quadrupole-Linear Ion Trap Tandem Mass Spectrometry.
This study might be beneficial to the quality assessment and control of PJR. Meanwhile, it might provide the basic information for confirming its optimal harvested period. PMID: 31366833 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Chen J, Tan M, Zou L, Liu X, Chen S, Shi J, Chen C, Wang C, Mei Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Sacran Hydrogel Film Containing Keratinocyte Growth Factor Accelerates Wound Healing by Stimulating Fibroblast Migration and Re-epithelization.
In this study, we fabricated sacran hydrogel film containing KGF (Sac/KGF-HF) and evaluated the effects of Sac/KGF-HF on fibroblasts migration and re-epithelialization process. We successfully prepared a homogenous and -amorphous Sac/KGF-HF by a casting method. In addition, Sac/KGF-HF had a high swelling ratio and flexibility. Sac/KGF-HF promoted a migration process of NIH3T3 cells and improved wound healing ability in mice with a percentage of wound closure reaching 90.4% at 9 d. Interestingly, the addition of KGF in Sac-HF considerably increased the number of epithelial cells compared to control, which is importan...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Wathoni N, Rusdiana T, Hasanah AN, Muhtadi A, Pratiwi ED, Mahmudah R, Mohammed AFA, Okajima M, Kaneko T, Arima H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Synthesis of Propargylic Ethers by Gold-Mediated Reaction of Terminal Alkynes with Acetals.
Abstract A gold-catalyzed introduction of various terminal alkynes to acetals was investigated. Extensive optimization of the reaction conditions revealed that thermally stable cationic gold catalysts bearing bulky ligands such as 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene 3-1H-benzo[d][1,2,3]triazolyl gold trifluoromethanesulfonate (IPrAu(BTZ-H)OTf) were particularly suitable for the reaction. Additionally, significant solvent effects were observed. Ether solvents such as tetrahydrofuran (THF), cyclo pentyl methyl ether (CPME), and 1,4-dioxane were effective for the reaction. Studies on the scope of substra...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Furuta M, Sugiyama K, Yamaguchi M, Ueda H, Tokuyama H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Study of the Inducible Cross-Linking Reaction to mRNA and the Effect on the Translation.
Abstract The 4-vinylpyrimidin-2-one nucleoside (T-vinyl) forms a cross-link with the RNA containing uracil at the complementary site at a high reaction rate. To obtain the stable T-vinyl derivative so that its reactivity is protected until it access to the target site, several derivatives were investigated, and the 2-thiopyridinyl- and 2-thiopyrimidinyl T-vinyl derivatives were determined to be good candidates. The 2-thiopyrimidinyl T-vinyl derivative was found to more efficiently cross-link with mRNA albeit having a better stability than the 2-thiopyridinyl T-vinyl derivative. The investigation using the lucifera...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Kikuta K, Taniguchi Y, Sasaki S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Detection of Selenocyanate in Biological Samples by HPLC with Fluorescence Detection Using K önig Reaction.
Detection of Selenocyanate in Biological Samples by HPLC with Fluorescence Detection Using König Reaction. Chem Pharm Bull (Tokyo). 2019;67(8):884-887 Authors: Mochizuki R, Higashi K, Okamoto Y, Abe H, Iwase H, Toida T Abstract We developed a simple and sensitive HPLC method for the determination of selenocyanate (SeCN-). The König reaction, which is generally used for the determination of cyanide and thiocyanate, was applied for the post-column detection, and using barbituric acid as a fluorogenic reagent made it possible to detect SeCN- with high sensitivity. The limits of detection (LOD) ...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Mochizuki R, Higashi K, Okamoto Y, Abe H, Iwase H, Toida T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Synthesis and Anticancer Activity of New ((Furan-2-yl)-1,3,4-thiadiazolyl)-1,3,4-oxadiazole Acyclic Sugar Derivatives.
Abstract New sugar hydrazones incorporating furan and/or 1,3,4-thiadiazole ring systems were synthesized by reaction of the corresponding hydrazide with different aldose sugars. Heterocyclization of the formed hydrazones afforded the derived acyclic nucleoside analogues possessing the 1,3,4-oxadiazoline as modified nucleobase via acetylation followed by the heterocyclization process. The anticancer activity of the synthesized compounds was studied against human liver carcinoma cell (HepG-2) and at human normal retina pigmented epithelium cells (RPE-1). High activities were revealed by compounds 3, 12 and 14 with I...
Source: Chemical and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Kassem AF, Nassar IF, Abdel-Aal MT, Awad HM, El-Sayed WA Tags: Chem Pharm Bull (Tokyo) Source Type: research

Lewis Base Assisted Lithium Br ønsted Base Catalysis: A New Entry for Catalytic Asymmetric Synthesis of β2,2-Amino Acids.
Lewis Base Assisted Lithium Brønsted Base Catalysis: A New Entry for Catalytic Asymmetric Synthesis of β2,2-Amino Acids. Chem Pharm Bull (Tokyo). 2019 Jul 25;: Authors: Amemiya F, Noda H, Shibasaki M Abstract A new catalytic system comprising chiral Ag complex and Li aryloxide/bisphosphine oxide is developed for the synthesis of β2,2-amino acids via direct asymmetric Mannich-type reaction of 4-subsituted isoxazolidin-5-ones. The Mannich adduct is a direct precursor of β-peptidic compounds otherwise difficult to obtain. PMID: 31341115 [PubMed - as supplied by publisher] (Sour...
Source: Chemical and Pharmaceutical Bulletin - July 25, 2019 Category: Drugs & Pharmacology Authors: Amemiya F, Noda H, Shibasaki M Tags: Chem Pharm Bull (Tokyo) Source Type: research

A Snapshot on the Current Status of Alzheimer's Disease, Treatment Perspectives, In-Vitro and In-Vivo Research Studies and Future Opportunities.
, Eroğlu H Abstract Alzheimer's Disease (AD) is one of the most challenging diseases faced by humankind. AD is still not classified as curable because of the complex structure of pathologies underlying it. As the mean life expectancy of the world population constantly increases, the prevalence of AD and treatment costs for AD also grow rapidly. Current state of the art for AD treatment mainly consists of palliative therapy aimed at providing symptomatic relief and improving the standard of living in patients with AD. However, different research groups are working on more effective and safe drug delivery options a...
Source: Chemical and Pharmaceutical Bulletin - July 24, 2019 Category: Drugs & Pharmacology Authors: Tezel G, Timur SS, Bozkurt İ, Türkoğlu ÖF, Eroğlu İ, Nemutlu E, Öner L, Eroğlu H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development of a membrane curvature-sensing peptide based on a structure-activity correlation study.
Abstract Membrane curvature formation is important for various biological processes such as cell motility, intracellular signal transmission, and cellular uptake of foreign substances. However, it remains still a challenging topic to visualize the membrane curvature formation on the cell membranes in real-time imaging. To develop and design membrane curvature-sensors, we focused on amphipathic helical peptides of proteins belonging to the Bin / Amphiphysin / Rvs (BAR) family as the starting point. BAR proteins individually have various characteristic structures that recognize different curvatures, and the derived ...
Source: Chemical and Pharmaceutical Bulletin - July 17, 2019 Category: Drugs & Pharmacology Authors: Kawano K, Ogushi M, Masuda T, Futaki S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Physical and Chemical Stability of Formulations Loaded with Taxifolin Tetra-octanoate.
Abstract Chemically stable ester derivatives of taxifolin have become a focus of interest for their role in the satisfactory effects on human health. Accordingly, the aim of this study was to evaluate the physical and chemical stability of different formulations containing 0.02% taxifolin tetra-octanoate, which was proved to possess higher inhibitory effect on tyrosinase activity compared with taxifolin in a cell-free system. In the studies of physical stability, a Brookfield viscometer was used to determine rheological behavior of formulations containing taxifolin tetra-octanoate, and a portable pH meter was used...
Source: Chemical and Pharmaceutical Bulletin - July 4, 2019 Category: Drugs & Pharmacology Authors: An HJ, Lee Y, Liu L, Lee S, Lee JD, Yi Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Discovery of Nuclear Receptor Ligands and Elucidation of Their Mechanisms of Action.
Abstract To develop potent ligands for the vitamin D receptor (VDR), we designed and synthesized a series of vitamin D analogues with and without 22-alkyl substituents. These analogues exhibited agonistic, partial agonistic, or antagonistic activity. To elucidate the mechanism of action of the analogues, we conducted crystal structure analyses of the ligand-binding domain (LBD) of VDR complexed with the analogues. The VDR-LBD/agonist complex exhibited precise interactions, which clearly explained VDR agonism. The VDR-LBD/partial agonist complex showed two conformers (agonist and antagonist binding conformers) in a...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Yamamoto K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Chemical Studies on Bioactive Natural Products Directed toward Development of Novel Antiinfective and Anticancer Medicines.
Abstract Natural products are still rich sources of clinically used medicines and lead compounds for them. This review summarizes chemical studies carried out by the author on natural products of microorganism origin, many of which were discovered at the Institute of Microbial Chemistry (BIKAKEN). Caprazamycin B is a liponucleoside antibiotic from which CPZEN-45, an antituberculosis agent with a unique mode of action, was developed. Intervenolin and leucinostatin A exert antiproliferative activity toward tumor cells in the presence of the corresponding stromal cells, which implies that the primary molecular target...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Watanabe T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Foreword.
PMID: 31257317 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Morikawa T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Effects of Benzophenones from Mango Leaves on Lipid Metabolism.
Abstract The mango tree (Mangifera indica L.) is a tropical, perennial, woody evergreen plant belonging to the Anacardiaceae. In traditional medicine, dried mango tree leaves were considered useful in treating diabetes and respiratory infections. In this paper, we review the phytochemical research on mango leaves and the mechanisms of benzophenones in lipid metabolism regulation. Thirty-six benzophenones have been isolated from mango leaves; among them, mangiferin is the major compound. Structure-activity relationships of benzophenones in lipid accumulation and the mechanisms of action of mangiferin in lipid metab...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Zhang Y, Chen Q, Liu MY, Ruan JY, Yu HY, Li J, Wang T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Natural Inhibitors on Over-Activation of Microglia from Herbals.
Abstract Neuroinflammation manifested by over-activation of microglial cells plays an essential role in neurodegenerative diseases. Short-term activation of microglia can be beneficial, but chronically activated microglia can aggravate neuronal dysfunction possibly by secreting potentially cytotoxic substances such as tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which can result in dysfunction and death of neurons. Therefore inhibiting over-activation of microglia and the production of cytotoxic intermediates may become an effective therapeutic approach for neuroinflammation. In this paper, we ...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Bai Z, Chen G, Li W, Hou Y, Li N Tags: Chem Pharm Bull (Tokyo) Source Type: research

Progress in Development of Interventions to Prevent Birth Defects in Diabetic Pregnancies.
Abstract Diabetic embryopathy is a diabetic complication, in which maternal hyperglycemia in early pregnancy causes birth defects in newborn infants. Under maternal diabetic conditions, hyperglycemia disturbs intracellular molecular activities and organelles functions. These include protein misfolding in the endoplasmic reticulum (ER), overproduction of reactive oxygen species (ROS) in mitochondria, and high levels of nitric oxide (NO). The resultant ER, oxidative, and nitrosative stresses activate apoptotic machinery to cause cell death in the embryo, ultimately resulting in developmental malformations. Based on ...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Han L, Jiang Z, Zheng X, Qiu J, Hu Y, Li X Tags: Chem Pharm Bull (Tokyo) Source Type: research

Relationship between Structural Characteristics and Plant Sources along with Pharmacology Research of Quassinoids.
Abstract Quassinoids, one kind of triterpenoids with multiple bioactivities such as anti-cancer, anti-malarial, anti-oxidative, anti-microbial, anti-diabetic, anti-viral, and anti-inflammatory effects, have drawn much attention in recent years. Between 2004 and 2018, the structural characteristics and plant sources of 190 quassinoids were reported. Herein, the structure-activity relationships (SARs) of quassinoids along with the anti-cancer mechanisms of four representative quassinoids, eurycomanone, bruceine D, dehydrobruceine B, and brusatol are discussed. This review might be useful for further research and dev...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Li Z, Ruan JY, Sun F, Yan JJ, Wang JL, Zhang ZX, Zhang Y, Wang T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Biofunctional Effects of Thiohemiaminal-Type Dimeric Sesquiterpene Alkaloids from Nuphar Plants.
Abstract Dimeric sesquiterpene thioalkaloids from the rhizomes of Nuphar pumilum exhibited immunosuppressive effects using a sheep erythrocyte plaque forming cell (PFC) assay, as well as an anti-metastasis effect, and rapid apoptosis-inducing effects in tumor cell lines. In particular, dimeric sesquiterpene thioalkaloids with a hydroxy group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial effects, whereas dimeric sesquiterpene thioalkaloids lacking the hydroxy group (thiobinupharidine, thionuphlutine B, 6'-hydroxythionuphlutine B, neothiobinupharidine, th...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Matsuda H, Nakamura S, Nakashima S, Fukaya M, Yoshikawa M Tags: Chem Pharm Bull (Tokyo) Source Type: research

A Review of Biologically Active Natural Products from a Desert Plant Cistanche tubulosa.
Abstract An Orobanchaceae plant Cistanche tubulosa (SCHENK) WIGHT (Kanka-nikujuyou in Japanese), which is one of the authorized plant resources as Cistanches Herba in both Japanese and Chinese Pharmacopoeias, is a perennial parasitic plant growing on roots of sand-fixing plants. The stems of C. tubulosa have traditionally been used for treatment of impotence, sterility, lumbago, and body weakness as well as a promoting agent of blood circulation. In recent years, Cistanches Herba has also been widely used as a health food supplement in Japan, China, and Southeast Asian countries. Here we review our recent studies ...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Morikawa T, Xie H, Pan Y, Ninomiya K, Yuan D, Jia X, Yoshikawa M, Nakamura S, Matsuda H, Muraoka O Tags: Chem Pharm Bull (Tokyo) Source Type: research

Transition in Longgu Surface Associated with Decoction Process of Keishikaryukotsuboreito.
Abstract We aim to attain the sustainable use of longgu and have investigated the significance of longgu in Keishikaryukotsuboreito (KRB) decoction. We have already reported that longgu alters compound profiles in KRB decoction and hypothesized that it does so by adsorbing foreign organic compounds into its superficial pores. In the present study, we focused on the adsorbability of organic materials onto longgu surface as the cause of component profile alteration. We analyzed the physical changes in longgu through the decoction process by measuring the adsorbed water on longgu surface. 1H magic angle spinning NMR ...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Oguri K, Ueda T, Takahashi K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Synthesis and Pharmacological Evaluation of 3-[(4-Oxo-4H-pyrido[3,2-e][1,3]thiazin-2-yl)(phenyl)amino]propanenitrile Derivatives as Orally Active AMPA Receptor Antagonists.
Abstract In our search for novel orally active α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, we found that conversion of an allyl group in the lead compound 2-[allyl(4-methylphenyl)amino]-4H-pyrido[3,2-e][1,3]thiazin-4-one (4) to a 2-cyanoethyl group significantly increased inhibitory activity against AMPA receptor-mediated kainate-induced toxicity in rat hippocampal cultures. Here, we synthesized 10 analogs bearing a 2-cyanoethyl group and administered them to mice to evaluate their anticonvulsant activity in maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Inami H, Shishikura JI, Yasunaga T, Hirano M, Kimura T, Yamashita H, Ohno K, Sakamoto S Tags: Chem Pharm Bull (Tokyo) Source Type: research