Foreword.
PMID: 32611992 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Nishida K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Bone-Targeted Drug Delivery Systems and Strategies for Treatment of Bone Metastasis.
Abstract Bone metastases can cause high morbidity and mortality, often developing as they advance, especially in patients with prostate and breast cancers. Most drugs are rarely distributed to the bone and are hence pharmacologically ineffective in treating bone metastases. The development of drug targeting technologies is required for the efficient treatment of bone metastases. To date, numerous bone-targeting ligands, including tetracyclines, bisphosphonates, aspartic acid, and aptamers have been developed and used for bone-targeted delivery of anti-tumor drugs, peptide/protein drugs, nucleic acid drugs, and dia...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Katsumi H, Yamashita S, Morishita M, Yamamoto A Tags: Chem Pharm Bull (Tokyo) Source Type: research

Recent Strategies for Targeted Brain Drug Delivery.
Abstract Because the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired. However, the development of therapies to treat some cerebral diseases is difficult because the blood-brain barrier (BBB) or blood-brain tumor barrier prevents drugs from entering the brain. Hence, drug delivery system (DDS) strategies are required to delive...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Ogawa K, Kato N, Kawakami S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Drug Delivery System for Refractory Cancer Therapy via an Endogenous Albumin Transport System.
Abstract A unique phenomenon in solid tumors, the enhanced permeability and retention (EPR) effect is now well known in the development of macromolecular anticancer therapy. However, cancers with low vascular permeability have posed a challenge for these EPR based therapeutic systems. An intrinsic vascular modulator, such as nitric oxide (NO), could augment the endogenous EPR effect. However, the most important aim has been to construct an effective NO delivery system for cancer. Since it is well known that human serum albumin is one of the most important endogenous NO transport proteins in human circulation, for ...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Ishima Y, Maruyama T, Otagiri M, Ishida T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Present Situation and Future Progress of Inhaled Lung Cancer Therapy: Necessity of Inhaled Formulations with Drug Delivery Functions.
Abstract Inhaled lung cancer therapy is promising because of direct and noninvasive drug delivery to the lungs with low potential for severe systemic toxicity. Thus chemotherapeutic drugs have been administered clinically by nebulization of solution or suspension formulations, which demonstrated their limited pulmonary absorption and relatively mild systemic toxicity. In all these clinical trials, however, there was no obviously superior anticancer efficacy in lung cancer patients even at the maximum doses of drugs limited by pulmonary toxicity. Therefore methods that deliver both higher anticancer efficacy and lo...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Okuda T, Okamoto H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Co-delivery Systems of Multiple Drugs Using Nanotechnology for Future Cancer Therapy.
Abstract Cancer treatments have improved significantly during the last decade but are not yet satisfactory. Combination therapy is often administered to improve efficacy and safety. Drug delivery systems can also improve efficacy and safety. To control the spatiotemporal distribution of drugs, nanotechnology involving liposomes, solid lipid nanoparticles, and polymeric micelles has been developed. Co-delivery systems of multiple drugs are a promising approach to combat cancer. Synergistic effects and reduced side effects are expected from the use of co-delivery systems. In this review, we summarize various co-deli...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Fumoto S, Nishida K Tags: Chem Pharm Bull (Tokyo) Source Type: research

A Series of Novel HDAC Inhibitors with Anthraquinone as a Cap Group.
Abstract Although anthraquinone derivatives possess significant antitumor activity, most of them also displayed those side effects like cardiotoxicity, mainly owing to their inhibition of topoisomerase II of DNA repair mechanisms. Our raised design strategy by switching therapeutic target from topoisomerase II to histone deacetylase (HDAC) has been applied to the design of anthraquinone derivatives in current study. Consequently, a series of novel HDAC inhibitors with a tricylic diketone of anthraquinone as a cap group have been synthesized. After screening and evaluation, compounds 4b, 4d, 7b and 7d have displaye...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Zou Y, Cao Z, Wang J, Chen X, Chen YQ, Li Y, Liu J, Zhao Y, Wang A, He B Tags: Chem Pharm Bull (Tokyo) Source Type: research

Synthesis and Structure-Activity Relationship of C-Phenyl D-Glucitol (TP0454614) Derivatives as Selective Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitors.
In this study we found a new method of synthesizing key intermediates 12 by a one-pot three-component condensation reaction and discovered C-phenyl D-glucitol 41j (TP0454614), which has>40-fold SGLT1 selectivity in vitro (IC50 26 nM for hSGLT1 and 1101 nM for hSGLT2). The results of our study have provided new insights into the structure-activity relationships (SARs) of the SGLT1 selectivity of C-glucitol derivatives. PMID: 32611999 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Kuroda S, Kobashi Y, Kawamura M, Kawabe K, Shiozawa F, Hamada M, Shimizu Y, Okumura-Kitajima L, Koretsune H, Kimura K, Yamamoto K, Kakinuma H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Discovery of a Novel Class of State-Dependent NaV1.7 Inhibitors for the Treatment of Neuropathic Pain.
Abstract The discovery of a novel class of state-dependent voltage-gated sodium channel (NaV)1.7 inhibitors is described. By the modification of amide or urethane bond in NaV1.7 blocker III, structure-activity relationship studies that led to the identification of novel NaV1.7 inhibitor 2i (DS01171986) were performed. Compound 2i exhibited state-dependent inhibition of NaV1.7 without NaV1.1, NaV1.5 or human ether-a-go-go related gene (hERG) liabilities at concentrations up to 100 μM. Further biological profiling successfully revealed that 2i possessed potent analgesic properties in a murine model of neur...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Tanaka K, Kobayashi H, Suzuki S, Shibuya S, Kimoto H, Domon Y, Kubota K, Kitano Y, Yokoyama T, Shimizugawa A, Koishi R, Fujiwara C, Asano D, Shinozuka T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Utilization of Diluted Compendial Media as Dissolution Test Solutions with Low Buffer Capacity for the Investigation of Dissolution Rate of Highly Soluble Immediate Release Drug Products.
This study indicated the importance of media buffer capacity as a factor inducing different dissolution between products of highly soluble active pharmaceutical ingredients. The diluted compendial media would be a useful alternative to biorelevant media for the detection of the different formulation performances depending on the buffer capacities. PMID: 32612001 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Yoshida H, Abe Y, Tomita N, Izutsu KI Tags: Chem Pharm Bull (Tokyo) Source Type: research

Flavanones from the Twigs and Barks of Artocarpus lakoocha Having Antiplasmodial and Anti-TB Activities.
Abstract Chromatographic separation of the acetone extracts from the twigs and barks of Artocarpus lakoocha led to the isolation of the one new flavanone, lakoochanone (1), together with eleven known compounds (2-12). Lakoochanone (1) and moracin C (4) exhibited weak antiplasmodial activity against Plasmodium falciparum Dd2 with IC50 values of 36.7 and 33.9 µM, respectively. Moreover, moracin C (4) and sanggenofuran B (5) showed cytotoxic activity against A2780 cell line with the respective IC50 values of 15.0 and 57.1 µM. In addition, cyclocommunin (7) displayed strong antimycobacterial ...
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Boonyaketgoson S, Du Y, Valenciano Murillo AL, Cassera MB, Kingston DGI, Trisuwan K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Syntheses of C2'-Fluorinated Analogs of Solamin.
Abstract The details of the total syntheses of C2'-fluorinated analogs of solamin, an antitumor annonaceous acetogenin, are described. Fluorine was enantioselectively introduced at the C2'-position by organocatalytic α-fluorination of the aldehyde according to a previously reported method. C2'-fluorinated solamin and its C2'-diastereomer were synthesized by the Sonogashira coupling of a tetrahydrofuran fragment and fluorine-containing γ-lactone fragments. PMID: 32612003 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Kojima N, Hayashi H, Iwasaki H, Yamashita M Tags: Chem Pharm Bull (Tokyo) Source Type: research

Synthesis of Nitriles via the Iodine-Mediated Dehydrosulfurization of Thioamides.
Abstract A simple general method for the synthesis of nitriles using the inexpensive and easy to handle iodine (I2) is described herein. The reaction of thioamides with I2 in the presence of triethylamine at room temperature under aerobic conditions afforded various nitriles bearing aryl, vinyl, and alkyl groups in good-to-excellent yields. This method was also effective for conversion from thioureas to cyanamides. PMID: 32612004 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - July 3, 2020 Category: Drugs & Pharmacology Authors: Murata Y, Iwasa H, Matsumura M, Yasuike S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Implementing PRED Subroutine of NONMEM for Versatile Pharmacokinetic Analysis using Fast Inversion of Laplace Transform (FILT).
In this study, we focus on extending the modeling functions of NONMEM, a standard software for PK and population pharmacokinetic (PPK) analyses, by adding the Fast Inversion of Laplace Transform (FILT) method, one of the representative numerical inverse Laplace transform methods. We implemented PREDFILT, a specialized PRED subroutine, which functions as an internal model unit in NONMEM to enable versatile FILT analysis with second-order precision. The calculation results of the compartment models and a dispersion model are in good agreement with the ordinary analytical solutions and theoretical values. Therefore, PREDFILT ...
Source: Chemical and Pharmaceutical Bulletin - July 1, 2020 Category: Drugs & Pharmacology Authors: Jin R, Hisaka A Tags: Chem Pharm Bull (Tokyo) Source Type: research

Collaborative Study to Validate Purity Determination by 1H quantitative NMR Spectroscopy by Using Internal Calibration Methodology.
Y Abstract Nuclear Magnetic Resonance (NMR) spectroscopy has recently been utilized to determine the absolute amounts of organic molecules with metrological traceability since signal intensity is directly proportional to the number of each nucleus in a molecule. The NMR methodology that uses hydrogen nucleus (1H) to quantify chemicals is called quantitative 1H NMR (1H qNMR). The quantitative method using 1H qNMR for determining the purity or content of chemicals has been adopted into some compendial guidelines and official standards. However, there are still few reports in the literature regarding validation of 1H...
Source: Chemical and Pharmaceutical Bulletin - June 19, 2020 Category: Drugs & Pharmacology Authors: Miura T, Sugimoto N, Bhavaraju S, Yamazaki T, Nishizaki Y, Liu Y, Bzhelyansky A, Amezcua C, Ray J, Zailer E, Diehl B, Gallo V, Todisco S, Ofuji K, Fujita K, Higano T, Geletneky C, Hausler T, Singh N, Yamamoto K, Kato T, Sawa R, Watanabe R, Iwamoto Y, Goda Tags: Chem Pharm Bull (Tokyo) Source Type: research

Fluorofunctionalizations of C-C Multiple Bonds and C-H Bonds.
This article discusses our contributions to this area. The first topic is on the trifluoromethylations of C-C multiple bonds using Togni reagent based on our working hypothesis that hypervalent iodine could be activated by coordination of the carbonyl moiety to the Lewis acid catalyst. The second topic relates to asymmetric fluorofunctionalization of alkenes. A newly designed phase-transfer catalyst consisting of a carboxylate anion functioning as a phase-transfer agent and a primary hydroxyl group as a site that captures the anionic substrate was revealed to be an effective catalyst for asymmetric fluorolactonization. Ins...
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Egami H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Enzymatic Stability of Myostatin Inhibitory 16-mer Peptides.
This study suggests that MIPE-1686 has a potential to serve as a long-lasting agent in vivo. PMID: 32475853 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Takayama K, Odagiri M, Taguchi A, Taniguchi A, Hayashi Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

A Combination of Cryopreservation and Kneading Maintains the Usability of Mohs Paste.
In this study, the combined use of cryopreservation and kneading was shown to improve long-term storage of Mohs paste. At 25°C, Mohs pastes solidified rapidly, and viscosity reached approximately 700 Pa·s 5 h after preparation. In contrast, cryopreservation at -20°C attenuated hardening of Mohs pastes, and kneading also decreased viscosity. The viscosity of Mohs pastes cotreated with cryopreservation and kneading after 7 months of storage was
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Okamoto H, Yoshikawa T, Takeuchi K, Deguchi S, Hatakenaka Y, Matsuoka H, Kawabata A, Nagai N Tags: Chem Pharm Bull (Tokyo) Source Type: research

Asymmetric Nitrogen-Containing Dimer from Aerial Parts of Mercurialis leiocarpa and Its Synthesis by Mimicking Generation Process through Radical Intermediates.
Abstract An asymmetric nitrogen-containing dimer, leiocarpanine A, was isolated from the aerial part of Mercurialis leiocarpa as a new compound. The new generation process of leiocarpanine A was estimated and a concise synthesis of leiocarpanine A could be detailed based on mimicking the generation process through the radical intermediates. In general, a lot of reaction step and organic reagents are required for the synthesis of asymmetric nitrogen-containing dimers. However, our new synthesis method enables a concise synthesis of asymmetric nitrogen-containing dimers through radical intermediates by only liquid-s...
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Kondo Y, Nakamura S, Ino S, Yamashita H, Nakashima S, Yamashita M, Matsuda H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development of Specific Fluorogenic Substrates for Human β-N-Acetyl-D-hexosaminidase A for Cell-Based Assays.
Development of Specific Fluorogenic Substrates for Human β-N-Acetyl-D-hexosaminidase A for Cell-Based Assays. Chem Pharm Bull (Tokyo). 2020;68(6):526-533 Authors: Miura K, Aoyama Y, Natsu Y, Koyama R, Hirano T, Nishio T, Hakamata W Abstract Inhibitors of human β-N-acetyl-D-hexosaminidase (hHEX) A and human O-GlcNAcase (hOGA) reportedly play roles in multiple diseases, suggesting their potential for pharmacological chaperone (PC) therapy of Sandhoff disease (SD) and Tay-Sachs disease (TSD), as lysosomal storage diseases, and Alzheimer's disease and progressive supranuclear palsy, respectively...
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Miura K, Aoyama Y, Natsu Y, Koyama R, Hirano T, Nishio T, Hakamata W Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development of Hydrophilic Polyacrylamide Gel-Based Condensing Reagents Comprised of Chlorotriazine.
Abstract Hydrophilic polyacrylamide gel-based triazine-type condensing reagents, PAG-Trz-Cl, have been developed. PAG-Trz-Cls were synthesized using a chlorotriazine with an acrylamide moiety, acrylamide, and N,N'-methylenebisacrylamide via both precipitation and solution polymerization. Because PAG-Trz-Cls adequately swell in aqueous media, the amidation between polar carboxylic acids and amines afforded the corresponding amides in good yields. PMID: 32475857 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Yamada K, Hirozawa S, Xia J, Kunishima M Tags: Chem Pharm Bull (Tokyo) Source Type: research

Preliminary Evaluation of Astatine-211-Labeled Bombesin Derivatives for Targeted Alpha Therapy.
This study presented a preliminary evaluation of 211At-labeled BBN derivative. Several nonradioactive iodine-introduced BBN derivatives (IB-BBNs) with different linkers were synthesized and their binding affinities measured. Because IB-3 exhibited a comparable affinity to native BBN, [211At]AB-3 was synthesized and the radiochemical yields of [211At]AB-3 was 28.2 ± 2.4%, with a radiochemical purity of>90%. The stability studies and cell internalization/externalization experiments were performed. [211At]AB-3 was taken up by cells and internalized; however, radioactivity effluxed from cells over time....
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Aoki M, Zhao S, Takahashi K, Washiyama K, Ukon N, Tan C, Shimoyama S, Nishijima KI, Ogawa K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Determining of the Water Quality of the Ping River at Different Seasons in Northern Thailand.
In this study, the water quality of the Ping river in Northern Thailand, including Chiang Mai and Lamphun provinces, was focused on and measured for three different seasons (summer, rainy, and winter seasons). Anions (F-, Cl-, NO2-, NO3-, and SO42-) and cations (Na+, Mg2+, Si4+, S6+, K+, and Ca2+) were qualified by an ion chromatograph and an inductively coupled plasma optical emission spectrometry, respectively. The concentration of anions and cations (except for Mg2+ and Ca2+) in the Ping river at upstream (countryside) locations were lower than that at downstream (closer main city) locations, which indicated that the fe...
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Ogata F, Saenjum C, Nagahashi E, Kobayashi Y, Nakamura T, Kawasaki N Tags: Chem Pharm Bull (Tokyo) Source Type: research

Catalytic Asymmetric 1,3-Dipolar Cycloaddition of α,β-Unsaturated Amide and Azomethine Imine.
Catalytic Asymmetric 1,3-Dipolar Cycloaddition of α,β-Unsaturated Amide and Azomethine Imine. Chem Pharm Bull (Tokyo). 2020;68(6):552-554 Authors: Li Z, Kumagai N, Shibasaki M Abstract α,β-Unsaturated amides were incorporated as viable dipolarophiles in a catalytic asymmetric 1,3-dipolar cycloaddition of azomethine imines. The use of a 7-azaindoline auxiliary was essential to acquire sufficient reactivity with excellent diastereoselectivity, likely due to the chelating activation of the amide by the In(III)/bishydroxamic acid complex. Although the enantioselectivity remains unsat...
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Li Z, Kumagai N, Shibasaki M Tags: Chem Pharm Bull (Tokyo) Source Type: research

Revisiting 2-Alkoxy-3-bromoindolines: Control C-2 vs. C-3 Elimination for Regioselective Synthesis of Alkoxyindoles.
Abstract The regioselective synthesis of both 2- and 3-alkoxyindoles from a common intermediate, 2-alkoxy-3-bromoindolines (ROBIN), is described. The 2-alkoxyindoles are obtained by a base-promoted regioselective elimination of HBr from ROBIN, whereas the synthesis of 3-alkoxyindoles is achieved by a silver-mediated alkoxylation followed by an acid-promoted elimination of alkoxide. This key elimination features the complete regioselectivity and no need for catalysts, that makes it have potential synthetic applications. Furthermore, this protocol is user friendly because ROBIN is able to be prepared from commercial...
Source: Chemical and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Abe T, Kosaka Y, Kawasaki T, Ohata Y, Yamashiro T, Yamada K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Redox State Control of Human Cytoglobin by Direct Electrochemical Method to Investigate its Function in Molecular Basis.
Abstract The direct electron transfer between human cytoglobin (Cygb) and the electrode surface, which would allow manipulating the oxidation states of the heme iron in Cygb, was first observed by immobilizing Cygb on a nanoporous gold (NPG) electrode via a carboxy-terminated alkanethiol. The voltammetric performances of the wild type and mutated Cygb-immobilized NPG electrodes were evaluated in the absence or presence of potential substrates. The obtained results demonstrated that the usefulness of the proposed method in understanding the function of Cygb in molecular basis. PMID: 32461519 [PubMed - as suppl...
Source: Chemical and Pharmaceutical Bulletin - May 26, 2020 Category: Drugs & Pharmacology Authors: Mie Y, Takahashi K, Torii R, Jingkai S, Tanaka T, Sueyoshi K, Tsujino H, Yamashita T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Potent Antibacterial Activity of Synthetic Peptides Designed from Salusin- β and HIV-1 Tat (49-57).
In this report, synthetic peptide conjugates of salusin-β and HIV-1 Tat (49-57) showed potent antibacterial activities against both Gram-positive Staphylococcus aureus NBRC 12732 and Gram-negative Escherichia coli NBRC 12734. The synthetic peptides also depolarized the cytoplasmic membrane of Escherichia coli NBRC 12734 as well as Staphylococcus aureus NBRC 12732. These results suggested that HIV-1 Tat (49-57) is a protein transduction domain or CPP that changes the interaction mode between salusin-β and the cell membrane of Escherichia coli NBRC 12734. By binding to HIV-1 Tat (49-57), salusin-β showed a bro...
Source: Chemical and Pharmaceutical Bulletin - May 22, 2020 Category: Drugs & Pharmacology Authors: Kimura M, Kosuge K, Ko Y, Kurosaki N, Tagawa N, Kato I, Uchida Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Facile synthesis of kwakhurin, a marker compound of Pueraria mirifica and its quantitative NMR analysis for standardization as a reagent.
In this study, we described the facile synthesis of KWA, a marker compound of P. mirifica. Our revised synthetic method produced KWA with shorter steps and higher yield than the reported method. Furthermore, the absolute purity of KWA was determined by quantitative NMR analysis for standardization as a reagent, and its purity was 92.62 ± 0.12%. PMID: 32434998 [PubMed - as supplied by publisher] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - May 21, 2020 Category: Drugs & Pharmacology Authors: Tsuji G, Yusa M, Masada S, Yokoo H, Hosoe J, Hakamatsuka T, Demizu Y, Uchiyama N Tags: Chem Pharm Bull (Tokyo) Source Type: research

The Endocytic Mechanism and Cytotoxicity of Boron-containing Vesicles.
Abstract A novel polymer (PEG2000-carborane), self-assembling into spherical vesicles (boron-containing vesicles, BCVs), could be quickly taken up by tumor cells and had an enhance stability in the bloodstream in previous study. To have more comprehensive understanding of BCVs, endocytic mechanism and cytotoxicity assessment were conducted. The results showed that BCVs were taken up in the intact form with cholesterol-dependent pathway during endocytosis, and BCVs exhibited nearly no cytotoxicity. BCVs could accumulate within tumors for at least 24 h. The data would provide reference information and guidance for B...
Source: Chemical and Pharmaceutical Bulletin - May 12, 2020 Category: Drugs & Pharmacology Authors: Wang D, Meng Y, Wang X, Xia G, Zhang Q Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development of Copper-Catalyzed Chemoselective Reactions.
Abstract Chemoselective reactions can contribute to streamlining synthesis of pharmaceuticals, agrochemicals, and other functional molecules by avoiding use of protecting groups. In this review, copper catalysts were demonstrated useful for developing two types of chemoselective reactions: C-C bond-forming reactions at an anomeric carbon of unprotected aldoses and difunctionalization reaction of C-C multiple bonds. The "soft" nucleophilic copper species exhibit orthogonal reactivity toward "hard" polar functional groups and preferentially react with "soft" functional groups. The catal...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Shimizu Y Tags: Chem Pharm Bull (Tokyo) Source Type: research

Magnolin Inhibits Proliferation and Invasion of Breast Cancer MDA-MB-231 Cells by Targeting the ERK1/2 Signaling Pathway.
In conclusion, MGL inhibits proliferation and invasion of and induces apoptosis in breast cancer cells through the ERK pathway. PMID: 32378540 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Wang J, Zhang S, Huang K, Shi L, Zhang Q Tags: Chem Pharm Bull (Tokyo) Source Type: research

Constituents of the Fruiting Body of Poisonous Mushroom Omphalotus japonicus.
Abstract Six new sesquiterpenes, tsukiyols A-C, neoilludin C, and 4-O-methylneoilludins A and B, were isolated from the fruiting body of Omphalotus japonicus (Kawam.) Kirchm. & O. K. Mill. Additionally, six known compounds, illudin S, neoilludins A-B, 5-hydroxydichomitol, ergosterolperoxide, and 3β,5α,9α-trihydroxyergosta-7,22-diene-6-one, were also obtained. Their chemical structures were determined with MS, IR, and NMR spectra and the absolute configurations of neoilludins A-C, 4-O-methylneoilludins A, and B were determined with electronic circular dichroism (ECD). Illudin S and 3β,5&al...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Aoki S, Aboshi T, Shiono Y, Kimura KI, Murata T, Arai D, Iizuka Y, Murayama T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Crystal Structure of Catechol O-Methyltransferase Complexed with Nitecapone.
Abstract Catechol O-methyltransferase (COMT) is known as an important drug-target protein in the field of Parkinson's disease. All clinically approved COMT inhibitors bring a 5-substituted-3-nitrocatechol ring as a pharmacophore, and they bind to COMT with S-adenosylmethionine (SAM) and an Mg2+ ion to form a quaternary complex (COMT/SAM/Mg2+/inhibitor). However, structural information about such quaternary complexes is only available for a few inhibitors. Here, a new crystal structure of COMT complexed with nitecapone (5), SAM and Mg2+ is revealed. Comparison of the structures of these complexes indicates that con...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Iijima H, Takebe K, Suzuki M, Kobayashi H, Takamiya T, Saito H, Niwa N, Kuwada-Kusunose T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Novel Indirect AMP-Activated Protein Kinase Activators: Identification of a Second-Generation Clinical Candidate with Improved Physicochemical Properties and Reduced hERG Inhibitory Activity.
This study reports the synthesis and evaluation of novel indirect AMP-activated protein kinase (AMPK) activators. The series of compounds selectively inhibited cell growth in several human breast cancer cell lines by activating AMPK. We performed back-up medicinal chemistry synthetic research on ASP4132, a previously reported as a compound for clinical development that acts as an indirect AMPK activator. This led to the successful identification of 4-({4-[5-({1-[(5-ethoxypyrazin-2-yl)methyl]-4-fluoropiperidin-4-yl}methoxy)-3-methylpyridine-2-carbonyl]piperazin-1-yl}methyl)benzonitrile succinate (27b), a potent, highly aque...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Kuramoto K, Sawada Y, Yamada T, Nagashima T, Ohnuki K, Shin T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Discovery of 1,3-Disubstituted 2,5-Diketopiperazine Derivatives as Potent Class I HDACs Inhibitors.
Abstract Histone deacetylases (HDACs) as attractive targets in many diseases therapies has been studied extensively, and its application in cancer research is the most important. Here, we developed a series of derivatives containing natural 2,5-diketopiperazine (DKP) skeleton. Several compounds exhibited distinct HDAC1 inhibitory activities, in particular 2a (IC50 = 405 nM). The selectivity profile for representative 2a indicated that this series of compounds had a preference for HDAC1-3. Additionally, 2a showed the best growth inhibitory activities against K562 and HL-60 tumor cell line with ...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Gong G, Qi J, Lv Y, Dong S, Cao C, Li D, Zhao R, Li Z, Chen X Tags: Chem Pharm Bull (Tokyo) Source Type: research

Instrument-Dependent Factors Affecting the Precision in the Atomic Force Microscopy Stiffness Measurement of Nanoscale Liposomes.
Abstract The mechanical strength (stiffness) of liposomes affects their cellular uptake efficiency and drug release in drug delivery processes. We recently developed a tip shape evaluation method for improving the precision of liposome stiffness measurement by quantitative imaging (QI)-mode atomic force microscopy (AFM). The present study applied our method to the widely-used AFM instruments equipped for intermittent contact (IC)-mode force curve measurements, and examined instrument-dependent factors that affect the liposome stiffness measurements. We demonstrated that the evaluation of the tip shape for cantilev...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Takechi-Haraya Y, Goda Y, Izutsu K, Sakai-Kato K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Ring-Opening Cyclization of Spirocyclopropanes Using Sulfoxonium Ylides.
Abstract Ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes using dimethylsulfoxonium methylide proceeded regioselectively to produce 2,3,4,6,7,8-hexahydro-5H-1-benzopyran-5-ones in good to high yields. The reactions of cycloheptane- and cyclopentane-1,3-dione-2-spirocyclopropanes could construct [7.6]- and [5.6]-fused ring systems. This reaction was also carried out using sulfoxonium ethylide, butylide, and benzylide, resulting in the formation of the corresponding 2,3-trans-disubstituted products in good to high yields, and it was shown that the dimethyl group can act as a dummy substituent. ...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Onuki Y, Nambu H, Yakura T Tags: Chem Pharm Bull (Tokyo) Source Type: research

DFT Study on the Biosynthesis of Preasperterpenoid A: Role of Secondary Carbocations in the Carbocation Cascade.
Abstract Preasperterpenoid A, featuring a 5/7/(3)6/5 pentacyclic structure, is a C25 sesterterpenoid produced by Penicillium verruculosum. The results of density functional calculations on putative biosynthetic carbocation cyclization/rearrangements leading to preasperterpenoid A revealed a highly concerted four-step cyclization mechanism. Interestingly, two secondary carbocation structures were obtained as minima, but appeared almost as shoulders in the energy profile, and may represent essentially transient structures during the highly concerted reaction. PMID: 32378547 [PubMed - in process] (Source: Chemic...
Source: Chemical and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Sato H, Yamazaki M, Uchiyama M Tags: Chem Pharm Bull (Tokyo) Source Type: research

Facile fluorescence dopamine detection strategy based on acid phosphatase (ACP) enzymatic oxidation dopamine to polydopamine.
Abstract Facile and effective detection of dopamine (DA) plays a significant role in current clinical applications. Substantially, special optical nanomaterials are important for fabricating easy-to-control, cheap, selective, and portable fluorescence DA sensors with superior performance. Herein, carbon dots (CDs) prepared from melting method were applied as signal to establish a simple but effective fluorescence strategy for DA determination based on the enzymatic activity of acid phosphatase (ACP), which induces DA to form polydopamine (pDA). The formed pDA caused by the enzymatic oxidization of ACP toward DA ca...
Source: Chemical and Pharmaceutical Bulletin - April 24, 2020 Category: Drugs & Pharmacology Authors: Pan J, Miao C, Chen Y, Ye J, Wang Z, Han W, Huang Z, Zheng Y, Weng S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita-Baylis-Hillman-Type Domino Reactions.
Abstract Organocatalytic enantioselective domino reactions are an extremely attractive methodology, as their use enables the construction of complex chiral skeletons from readily available starting materials in two or more steps by a single operation under mild reaction conditions. Thus, these reactions can save both the quantity of chemicals and length of time typically required for the isolation and/or purification of synthetic intermediates. Additionally, no metal contamination of the products occurs, given that organocatalysts include no expensive or toxic metals. The aza-Morita-Baylis-Hillman (aza-MBH) reacti...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Takizawa S Tags: Chem Pharm Bull (Tokyo) Source Type: research

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood-Brain Barrier Using Receptor-Mediated Transcytosis.
Abstract Discriminatory drug delivery into target cells is essential to effectively elicit the drug activity and to avoid off-target side effects; however, transporting drugs across the cell membrane is difficult due to factors such as molecular size, hydrophilicity, intercellular adhesiveness, and efflux transporters, particularly, in the brain capillary endothelial cells. Drug delivery into the brain is blocked by the blood-brain barrier (BBB). Thus, developing drugs for the central nervous system (CNS) diseases remains a challenge. The approach based on receptor-mediated transcytosis (RMT) can overcome this imp...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Tashima T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Effect of Solution Composition on Impurity Profile of the Crystallized Product in Oiling-Out Crystallization.
In this study, we explored the effect of EtOH solution composition on impurity profile of the crystallized product in oiling-out crystallization, and found that the low content of Imp-B in the EtOH solution, the higher content of Imp-C in the crystallized product. Our finding revealed that not only oiling-out but also Imp-B played a key role in inhibiting the incorporation of Imp-C into the crystals. PMID: 32238650 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Tanaka K, Takiyama H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Adsorption of Phosphate Ions on Novel Mg/Fe/Al Hydroxides (MFA) Prepared at Different Mg2+/Fe3+/Al3+ Ratios.
In this study, we prepared novel Mg/Fe/Al hydroxides (MFA series: denoted by MFA1, MFA2, MF, and MA) and investigated their properties using scanning electron microscopy, X-ray diffraction, the specific surface area, and amount of hydroxyl groups. Additionally, the phosphate adsorption capabilities of the MFA series or Fe-Mg type hydrotalcites (FHT3.0 and FHT5.0) were evaluated by examining the effects of the solution pH and contact time, and analyzing the adsorption isotherm and desorption characteristics. In MFA1, a strong correlation exists between the amount of adsorbed phosphate ions and surface hydroxyl groups, with ...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Nakamura T, Nagafuji R, Ogata F, Kawasaki N Tags: Chem Pharm Bull (Tokyo) Source Type: research

Design and Synthesis of 2-(1-Alkylaminoalkyl)pyrazolo[1,5-a]pyrimidines as New Respiratory Syncytial Virus Fusion Protein Inhibitors.
Abstract Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections and a significant pathogen for both adults and children. Although two drugs have been approved for the treatment of RSV infections, the low therapeutic index of these drugs have led pharmaceutical companies to develop safe and effective small-molecule anti-RSV drugs. The pyrazolo[1,5-a]pyrimidine series of compounds containing a piperidine ring at the 2-position of the pyrazolo[1,5-a]pyrimidine scaffold are known as candidate RSV fusion (F) protein inhibitor drugs, such as presatovir and P3. The piperi...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Yamaguchi-Sasaki T, Tamura Y, Ogata Y, Kawaguchi T, Kurosaka J, Sugaya Y, Iwakiri K, Busujima T, Takahashi R, Ueda-Yonemoto N, Tanigawa E, Abe-Kumasaka T, Sugiyama H, Kanuma K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Preparation of Biodegradable PLGA-Nanoparticles Used for pH-Sensitive Intracellular Delivery of an Anti-inflammatory Bacterial Toxin to Macrophages.
Abstract Poly(D,L-lactide-co-glycolic) acid (PLGA) is a synthetic copolymer that has been used to design micro/nanoparticles as a carrier for macromolecules, such as protein and nucleic acids, that can be internalized by the endocytosis pathway. However, it is difficult to control the intracellular delivery to target organelles. Here we report an intracellular delivery system of nanoparticles modified with bacterial cytotoxins to the endoplasmic reticulum (ER) and anti-inflammatory activity of the nanoparticles. Subtilase cytotoxin (SubAB) is a bacterial toxin in certain enterohemorrhagic Escherichia coli (EHEC) s...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Harada A, Tsutsuki H, Zhang T, Lee R, Yahiro K, Sawa T, Niidome T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Design, Synthesis, Biological Evaluation and Inhibition Mechanism of 3-/4-Alkoxy Phenylethylidenethiosemicarbazides as New, Potent and Safe Tyrosinase Inhibitors.
In this study, thirty-nine 3-/4-alkoxyphenylethylidenethiosemicarbazides were synthesized as novel tyrosinase inhibitors based on structure-based molecular design. Our experimental results demonstrated that thirty-one of them possess remarkable tyrosinase inhibitory activities with IC50 value below 1 µM, and 5a, 6e, 6g and 6t did not display any toxicity to 293T cell line at the concentration of 1000 µmol/L. According to the inhibitory activities, several compounds were selected for detail investigation on the structure-activity relationships (SARs), mechanisms of enzyme inhibition, inhibitory kin...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Song S, Mai Y, Shi H, Liao B, Wang F Tags: Chem Pharm Bull (Tokyo) Source Type: research

Total Syntheses and Cytotoxic Evaluations of Cryptolactones A1, A2, B1, B2, and Their Derivatives.
Abstract The cryptolactones A1, A2, B1, and B2 isolated from a Cryptomyzus sp. aphid were synthesized via the Mukaiyama aldol reaction and olefin metathesis. Their antipodes and derivatives were also synthesized by the same strategy to investigate structure-activity relationships. These compounds exhibited cytotoxic activity against human promyelocytic leukemia HL-60 cells with IC50 values of 2.1-42 µM. PMID: 32238655 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Inai M, Oguri Y, Horikawa M, Kaku H, Suzuki S, Kitamura K, Tsunoda T Tags: Chem Pharm Bull (Tokyo) Source Type: research

Nucleophilic Addition Reaction with Dearomatization of Naphthalene Ring.
Abstract Various aromatic lactones have been synthesized and their regioselectivity (1,2-addition vs. 1,4- or 1,6-addition) investigated in reactions with organolithium species, particularly n-BuLi and sec-BuLi. The regioselectivity varied greatly depending on various factors, such as the bulkiness of both substrates and organolithium species, and types of solvent and cosolvent. In particular, 1,4-addition with dearomatization occurred preferentially using sec-BuLi as the nucleophile in tetrahydrofuran (THF) with hexamethylphosphoramide (HMPA) or N,N'-dimethylpropyleneurea (DMPU) as cosolvent. For sec-BuLi, the re...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Sasaki H, Kiyotaki K, Imayoshi A, Tsubaki K Tags: Chem Pharm Bull (Tokyo) Source Type: research

Degradation Pathway of a Taxane Derivative DS80100717 Drug Substance and Drug Product.
Abstract The degradation pathway of a taxane derivative and anticancer agent, DS80100717, was investigated. Several degradants were generated under acidic, basic, and oxidative stress conditions in solution. The chemical structures of eight degradants of DS80100717 were elucidated using MS and NMR. The major degradant of the DS80100717 drug substance derived by heating in solid-state was the N-oxide form via oxidation and C2'-epimer of the side chain via acid hydrolysis. We proposed previously unreported degradation pathways of DS80100717 with taxane derivatives such as paclitaxel, docetaxel, and cabazitaxel. ...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Tamura K, Ono M, Kawabe T, Ohara M, Yonemochi E Tags: Chem Pharm Bull (Tokyo) Source Type: research

Development of Photoswitchable Estrogen Receptor Ligands.
Abstract Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on their conformational change by photo-irradiation. Previously, we have reported several types of selective estrogen receptor (ER) modulators based on diphenylmethane skeleton. To develop novel photopharmacological reagents, we designed and synthesized a set of ER ligands based on azobenzene skeleton, which can switch its conformation following UV irradiation. Our results showed that after UV irradiation, the Z-form of the synthesized compou...
Source: Chemical and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Tsuchiya K, Umeno T, Tsuji G, Yokoo H, Tanaka M, Fukuhara K, Demizu Y, Misawa T Tags: Chem Pharm Bull (Tokyo) Source Type: research