Biological membranes are an important target for
molecular design. Properly designed membrane-interacting peptides can induce
physicochemical and physiological responses in cell membrane and modulate cell
structure and function.
Previously, the authors developed a
cyclization reaction-based turn-on probe (TCC probe) for protein labeling. The
TCC probe is characterized by its ability to construct coumarin structures
easily by conjugate addition to the ynone moiety, but the reactivity of the
probe becomes poor when attempting to improve the fluorescence properties. The
authors improved the reactivity by increasing the electron-withdrawing property
of the leaving ester group and succeeded in constructing the coumarin skeleton
with good yields. These results suggest an easy method to introduce a coumarin
skeleton with good fluorescence properties.
Quality by design (QbD) is an
essential concept for modern manufacturing processes of pharmaceutical
products. Understanding the science behind manufacturing processes is crucial;
however, the complexity of the manufacturing processes makes implementing QbD
challenging. In this study, structural equation modeling (SEM) was applied to
understand the causal relationships between variables such as process
parameters, material attributes, and quality attributes. Based on SEM analysis,
a model composed of the above-mentioned variables and their latent factors without
including observational data was identified. The results indicate that SEM
analysis could be useful for implementing QbD for the manufacturing processes
of pharmaceutical products.
of the wide range of protein-protein interaction surfaces, it is important to
develop molecules that satisfy the intrinsic shape recognition of the partner
protein. The authors have previously shown that a stable non-naturally
occurring helix trimer of all trans-amide-bonded bicyclic β-amino acid inhibits
the p53-MDM2/MDMX-helix-helix interaction that plays a role in regulating p53
function. The authors showed herein that modification of the
C-terminal/N-terminal residues improved the inhibitory activity, and confirmed
that these peptides are membrane-permeable p53-MDM2/MDMX interaction
antagonists and can rescue p53 function in cells.
bioactivities of natural products are often beyond human knowledge and
imagination. In this article, the author developed original screening methods
based on protein binding activity. Protein beads method and protein plate
method were described. Protein beads method led to the discovery of neural stem
cell differentiation activators which inhibited Hes1 dimer formation as a new
mechanism. The author also developed protein plate method for protein-protein
interaction inhibitors to find new cancer drug candidates. Because protein
binding ability is tightly related to bioactivity, protein-based natural
products isolation is a powerful means to find new candidate medicines.
A cooperative catalyst comprising a soft Lewis acid/hard Brønsted
base enabled chemoselective activation of a hydroxyl group over an amino group.
The present chemoselective
catalysis could be applicable for a variety of amino alcohols, including
pharmaceuticals, without requiring a tedious
protection-deprotection process. Chemoselective enolization and subsequent α-functionalization
of carboxylic acid derivatives were also achieved by a redox active catalyst through
the radical process, providing unnatural α-amino/hydroxy
acid derivatives bearing a complex carbon framework and a diverse set of
functionalities. The present chemoselective catalysis described herein offers new
opportunities to expand the chemical space for innovative drug discovery
The optical property of fluorescent unit-conjugated
aliphatic oxaboroles has been investigated in this featured article. The authors
described the synthesis of fluorescent-oxaboroles by originally developed
methods and the optical behavior of the boroles with various sugars. The
oxaboroles provide good fluorescence quantum yields and selective recognition
toward D-ribose and D-ribose-containing molecules. The molecular recognition
induced significant fluorescence quenching. The authors also revealed the positive
correlation between the LUMO energy of the oxaborole and the relative
fluorescence intensity. The property of the boroles showed the possibility of
the boron-based NAD sensor probe.
Quantitative evaluation for
bitterness of pediatric medicine is essential for adherence.
The authors proposed criteria, change in concentration-dependent
potential (CCDP), dose-response slope of the sensor outputs of active
pharmaceutical ingredients measured by an
artificial taste sensor, which is new and useful bitterness evaluation index
for 48 pediatric medicines from the recent edition of the
WHO model list of essential medicines for children (7th ed., 2019). CCDP by individual
basic bitterness sensor well correlated to various physicochemical factors
related hydrophilicity and hydrophobicity. Therefore, CCDP proved to be useful
as a bitterness evaluation index of APIs in pediatric medicines.
Novel 25 derivatives of puberulic acid were synthesized by utilizing the
authors’ total synthetic route. According to previous structure-activity
relationships information, they focused on the carboxylic acid moiety in puberulic
acid and converted it into the corresponding esters, amides and ketones. Antimalarial
evaluations in vitro and in vivo of these derivatives were
carried out and revealed detailed SAR information. It was clarified that
several ester and ketone derivatives conserve strong antimalarial activity
similar to that of puberulic acid without any obvious toxicity in oral dose of
review aims to achieve a comprehensive and up-to-date investigation in the
phytochemistry and pharmacology of Rosa laevigata Michx.. To date, phytochemical
investigation has exposed the presence of triterpenoids, flavonoids, tannins,
ligands and polysaccharides in this plant. The crude extracts and the purified compounds have
demonstrated various pharmacological effects
in vitro and in vivo. In conclusion, the chemical profiles together with the modern
pharmacological properties have been adequately summarized. These evidences have
revealed this plant to be a valuable source for therapeutic foodstuff and more attention should be paid to a better utilization
of this plant.
fungal meroterpenoids are promising drug seed
compounds. To obtain unnatural, novel meroterpene scaffolds, the authors tested
combinatorial biosynthesis by co-expressing functionally distinct terpene
cyclase (TPC) genes, pyr4, ascF, andB, or cdmG, with the
biosynthetic genes for the production of a TPC substrate, (10’R)-epoxyfarnesyl-dimethylorsellinic
acid-3,5-methyl ester, in Aspergillus
oryzae NSAR1 as a heterologous host. As a result, all of the tested TPCs
afforded the same two novel mono-cyclization products. This study provides
important information on the substrate scope of the TPCs, and will contribute
to the production of unnatural, novel molecules for future drug discovery.
authors developed solifenacin succinate functional drug particles embedded in a
gelling–swelling layer (PEGS) made of a three-layer structure consisting of a
core drug layer, a gelling–swelling layer, by which both adequate taste-masking
of drug and rapid drug elution were successfully achieved. They also optimized
incorporation of above PEGS into orally disintegrating tablets (ODTs), by usage
of a fibre-shaped microcrystalline cellulose with poor fluidity, which improved
the content uniformity of the ODTs, as the crystal fibres became entangled with
the PEGS and other additives.
this taste masking system is so unique and propose new platform for taste
A methanol extract from the underground part of
Calanthe discolor Lindl.
(Orchidaceae) demonstrated significant proliferative activity against human hair follicle dermal
papilla cells (HFDPC). Through bioassay-guided separation of the
extract, a new indole glycoside named 6′-O-b-D-apiofuranosylindican
was isolated along with six known compounds including three indole glycosides. Among
the isolates, three indole glycoside such as 6′-O-b-D-apiofuranosylindican,
glucoindican, and calanthoside showed significant proliferative activity.
Furthermore, these active indole glycosides upregulated the expression of VEGF
and FGF-7 mRNA and protein in HFDPC, which could be the mechanism of their proliferative
manuscript reports aerobic oxidation of primary alcohols into aldehydes with
nitroxyl radical/copper catalysis. The reaction method reported herein features
that the optimum nitroxyl radical/copper salt catalyst combinations differ
depending on the substrate.
express this feature, the catalytic reaction field is represented as a circus
tent with three shapes of windows, namely, circle, triangle, and square. Copper
plates with different nitroxyl radicals are placed under each of the windows,
which indicates different nitroxyl radical/copper salt catalyst combinations.
Different alcohol substrates are represented in different forms, namely,
sphere, tetrahedron, cube. The sphere, tetrahedral, and cubic alcohols pass
through the circular, triangular, and square windows, respectively, to be
oxidized into aldehydes.
Non-canonical amino acid derivatives and the
peptides containing such structures are regarded as the attractive scaffold of
novel drug candidates. In this featured article, the author describes the
development of novel methodologies for the synthesis of them, involving (1)
catalytic asymmetric 1,2-addition of N-2-nitrophenylsulfenyl
imines, (2) direct chemical transformation such as ring-closing metathesis or
asymmetric Friedel–Crafts reaction using hydrophobic anchor-tagged peptidic
substrates. The development of (3) novel recyclable organocatalyst by combining
the catalytic motif and hydrophobic anchor is also described.
The authors report novel positive allosteric modulators
(PAMs) of M3 muscarinic acetylcholine receptor (mAChR) with N-pyrimidyl/pyridyl-2-thiazolamine scaffold. The structureactivity
relationships study was rationalized using conformational analyses based on
intramolecular interactions, demonstrating that a unique sulfur-nitrogen
nonbonding interaction in the N-pyrimidyl/pyridyl-2-thiazolamine
moiety is essential for activity. Newly identified compound 3g showed
potent in vitro PAM activity for the M3 mAChR with excellent
subtype selectivity. Compound 3g also showed a distinct pharmacological
effect on isolated smooth muscle tissue from rat bladder and favorable
pharmacokinetics profiles, suggesting its potential as a chemical tool for
probing the M3 mAChR in further research.
Cycloalkanes with small ring sizes (such as
cyclopropanes and cyclobutanes) constitute a basic structural framework of a
wide range of natural products. Cycloalkanes play an important role in organic
synthesis as they can take part in various types of reactions. The high
reactivities can be attributed to the angle and torsional strains. The
authors have been interested in the reactivities of small-ring compounds. The reaction between 3-oxa-2-oxobicyclo[4.2.0]oct-4-ene-1-carboxylate
and dimethylsulfoxonium methylide afforded 3a,4,5,7a-Tetrahydro-7-hydroxy-benzofuran-6-carboxylate
and/or 2-hydroxybicyclo[4.1.0]hept-2-ene-3-carboxylate. A plausible reaction mechanism
has been shown.
Oral mucositis is one of the most
common adverse effects of radiation and chemotherapy in treatments of cancers. A mouthwash containing
often used for the prevention
and treatment of oral mucositis. In this study, the authors indicated the disappearance
time and palatability in the oral cavities of healthy volunteers in placebo foam
formulations. In addition, foam formulations of drugs for use as a prevention and treatment of oral mucositis were prepared. This is the first report in regard to foam formulations containing drugs for oral mucositis, and these formulations could
be potentially useful in treatments of cancers.
To evaluate the impact of air pollutants
long-range transported from the Asian continent
on the atmospheric environment in Japan, a background site in the top of Noto
peninsula, the Kanazawa University Wajima Air Monitoring Station (KUWAMS), has
been used for continuous observation since 2004. Among the numerous reports on
air pollution during the COVID-19 pandemic, this article proves for the first
time that the implementation of the lockdown policy in China reduced both the
air pollution in domestic China and that involved in the long-range transport
to KUWAMS, including fine (PM2.5) and ultrafine particulates (PM1.0),
Organic Carbon (OC) and Element Carbon (EC).
site-selective transformation provides a powerful strategy for synthesizing
complex and diverse multi-functionalized molecules. In this article, the first
total syntheses of O-3’-acyl α-bisabolol
β-D-fucopyranoside natural products and their analogues by using boronic
acid-catalyzed site-selective acylation in the final stage is described. This
approach allows us to construct compound libraries for the purpose of
structure–activity relationship studies. The cover art illuminates key feature
of this work by characteristic chemical transformation.