Actinobacteria are the rich source of natural products while the large parts of biosynthetic gene clusters (BGCs) are silent under the standard culture conditions. The authors previously demonstrated that co-culture with mycolic acid-containing bacterium (MACB) effectively activates the silent BGCs in actinobacteria. In this study, the authors investigated the actinobacterium which produces a polyene macrolactam, mirilactam A. The authors tested co-culture of the mirilactam A producer strain with MACB, and successfully obtained three novel polycyclic macrolactams, mirilactams C-E, by activating silent biosynthetic genes responsible for the epoxidation and cyclization of the polyene mirilactam A.
The genus Dendrobium (Orchidaceae) is comprised of more than 1,000 species and divided into two major groups, Asian and Australasian clades. There are many ethnobotanical important species in this genus and various phenanthrenes and bibenzyl derivatives have been isolated from Dendrobium in previous studies. Secondary metabolites produced by species of the Australasian clade have not been studied well, even though several species of this group have also been used as traditional herbal remedies. The authors provide an overview of secondary metabolites of Dendrobium by combined non-target metabolomics and multivariate analysis, and identified characteristic compounds from several closely related Australasian species.
article describes the estimation of the diffusion coefficients of sugars and a
related compound. A simple and handy
experimental system with agar-gel was built and used to observe diffusion of small
molecules. The correlation formulas derived from computer simulations of the
experimental diffusion system were then applied to estimate diffusion
coefficients. The values obtained for these coefficients agree reasonably well
with those published in the literature. This finding supports the efficacy of the
approach for estimating diffusion coefficients, leading to the elucidation of
the diffusion coefficients of galactose, trehalose and glycerol.
The antiparallel triplex DNA is formed by the interaction between purine-rich triplex forming oligonucleotides (TFOs) and the homo-purine region within a duplex DNA. The formation of such a structure with the genome DNA promises to control the gene expression in a living cell. In this paper, in an attempt to enhance the stability of the triplex DNAs, the authors have designed and synthesized the N2-arylated deoxyguanosine derivatives. The TFOs containing N2-phenyl-2′-deoxyguanosine (PhdG) showed a stable and selective triplex DNA formation with the GC base pair as compared to the natural dG/GC triplet.
Dolastatin 16 is a cyclic depsipeptide isolated from cyanobacterium Lyngbya majuscula, however, its bioactivity has been a historical question. In this study, FKBP1A was predicted as a potential target of dolastatin 16 via PharmMapper as well as verified using chemical-protein interactome (CPI) and molecular docking. The lowest binding energy of dolastatin 16-FKBP1A complex was -7.4 kcal/mol. The ligand dolastatin 16 formed three hydrogen bonds and seven hydrophobic interactions within the active site residues. And the pharmacophore model was shown feasibly matching with the molecular feature of dolastatin 16.
Photographs of tropical and subtropical plants of Madagascar, Thailand, Vietnam, Indonesia and Okinawa, Japan by courtesy of the authors. And some chemical structures of new compounds isolated from these plants are shown. Upper left: Macaranga tanarius and a prenylflavanone, Upper middle: Senna siamea, Upper right: Croton tonkinensis and an ent-Kaurane diterpene, Middle left: Rhinacanthus nasutus, Central middle: Baobab; Adansonia grandidieri, Middle right: Impatiens balsamina, Lower left: Artemisia roxburghiana and X-ray crystallography of a guaianolide, Lower middle: Justicia gendarusa, Lower right: Croton cascarilloides and a plausible biosynthetic pathway of new skeletons.
The authors designed and synthesized a series of cell-penetrating peptides containing cationic proline derivatives (ProGu) that exhibited responsive changes in their secondary structures to the cellular environment. Effects of the peptide length and steric arrangement of the side chain in cationic proline derivatives [Pro4SGu and Pro4RGu] on their secondary structures and cell membrane permeability were investigated. Moreover, peptides 3 and 8 exhibited efficient intracellular delivery of plasmid DNA. These results indicate that the peptides containing cationic proline derivatives could be a useful tool to deliver the hydrophilic biomolecules into the cells.
A practical Pd-catalyzed carbonylation of (hetero)aryl bromides using a crystalline carbon monoxide (CO) surrogate, 2,4,6-trichlorophenyl formate (TCPF), was developed. This reaction proceeds without the slow addition technique that was previously required and with a low catalyst loading (1 mol%) on a gram scale. The utility of this Pd-catalyzed external-CO-free carbonylation using TCPF was demonstrated in the synthesis of a histone deacetylase inhibitor.
In this study, scale-up experiments of the lubricant mixing processes were conducted for V-type blenders under the same condition of fill level and Froude number. Three scales of V-type blender were used for the scale-up experiment. However, the physical properties of them were not corresponded either mixing time or number of revolution. Thus, the DEM simulations of three scales of V-type blender mixing were conducted to find the scale-up factor. As a result, it was found that a scale-up simulation based on the travel distance of particles is valid for lubricant mixing scale-up processes.
The authors established a HPLC-Q-TOF-MS method for rapid analysis of alkaloids in KHR98 (the extract of Uncaria rhynchophylla). A total of eight compounds, including four known alkaloids and four unknown components, were detected and identified. The structural information and fragmentation pathways of eight components were interpreted. A precise and sensitive HPLC-MS method was validated to simultaneously determine these substances. This study shed light on the standardization and quality control of the KHR98 and provided a foundation for the further research on pharmacology, follow-up clinical research and New Drug Applications.
This paper describes the development and characteristics of Fe–Mg type hydrotalcite (Fe-HT) with different molar ratios and the adsorption behavior of nitrite and nitrate ions onto that in aqueous solution. It is found that the adsorption capability onto Fe-HT of nitrite and nitrate ions is larger than that onto Al-Mg type hydrotalcite (Al-HT). Moreover, the adsorption mechanism of nitrite and nitrate ions involves the ion exchange process with chloride ions. We prepared and discovered Fe-HT, which is the novel adsorbent for the removal of inorganic nitrogen ions for water environment purification.
The desolvation of human serum albumin (HSA) using ethanol followed by stabilization through crosslinking with glutaraldehyde is a common technique for preparing HSA nanoparticles. Doxorubicin-loaded HSA nanoparticles with a size optimum for delivery to tumor tissues could be prepared by desolvating at a higher pH and intracellular uptake of the nanoparticles in cancer cells could be observed. HSA nanoparticles were also prepared with other anthracycline derivatives, and all showed cytotoxicity in cancer cells. However, the efficiency of drug loading and dissolution rate were different among them possibly due to the differences in the type of association of the drugs on nanoparticles.
Paeoniae Radix, the dried root of Paeonia lactiflora Pallas, is frequently used in traditional Japanese medicine. This paper studied the metallomic profiles between Paeoniae Radix (crude drugs) and the dried roots of various cultivar strains of Paeonia lactiflora produced in Japan in order to seek the strain which derives both commercially variable flowers and medicinally available roots to promote the domestic production. The results suggest that those cultivars can be alternatives to crude drugs from the point of view of metallomics.
The number of probiotic cells in the formulation of the dietary supplement that contains probiotic culture Lactobacillus plantarum 299v, sucrosomal iron, and vitamin C was optimized. Optimal quantity of active component Lactobacillus plantarum 299v of 50 mg was selected (50 mg) and expiration date was also determined by the analysis of the number of viable probiotic cells. The effects of the selected formulation were confirmed by the clinical study that presented better iron absorption in the subjects who used capsules with Lactobacillus plantarum 299v together with iron and vitamin C.
This paper describes the total synthesis of polyketide natural product trichodermatide A. The late-stage Isayama-Mukaiyama hydration of an enol ether using Co(acac)2 gives the desired product chemo-, regio-, and diastereoselectively. In addition, the unique cobalt-catalyzed hydroelementation reactions (C–X (X = O, N, C, F) bond formation) of olefins involving a cobalt-salen complex, N-fluoro-2,4,6-trimethylpyridinium salt, and a silane reagent occurs with good functional group tolerance via a carbocationic or carbon radical species.
This paper describes the development of
triazine-based benzylating reagents, 4-(4,6-di-t-butyl-1,3,5-triazin-2-yl)-4-benzylmorpholinium triflate, and
related derivatives. These reagents generate benzyl triflate (BnOTf) as a
benzyl cation equivalent upon heating the solution to 40 °C under neutral
conditions. The incorporation of a bulky t-butyl
group into the triazine ring of the reagents prevents the formation of N-benzyltriaziniums, which are byproducts
from the reaction of BnOTf and co-products, morpholinotriazine derivatives. O-Benzylation of various alcohols with a
stoichiometric amount of these reagents proceeded in good yields.
This article describes the discovery of
potent pyrimidoindazoles as PDE10A inhibitors by using the method of
fragment-based drug discovery (FBDD). The authors made use of X-ray analysis
well to obtain PDE10A inhibitors. In addition, they designed well-balanced
compounds in light of physicochemical property and inhibitory activity. This
study showed that FBDD approach is effective for the discovery of PDE10A
Methyl-b-cyclodextrin (M-b-CyD) exhibits an antitumor activity,
although its tumor-selectivity is low.
Meanwhile, hyaluronic acid (HA) is known as a promising tumor
targeting ligand, because various cancer cells overexpress CD44, a HA-binding glycoprotein. In this study, to develop a tumor-selective
delivery system for M-b-CyD, the authors designed
a supramolecular complex of M-b-CyD with adamantane-grafted HA (Ad-HA/M-b-CyD) and evaluated it as a tumor-selective antitumor
agent. Eventually, Ad-HA/M-b-CyD showed the superior cytotoxic activity via CD44-mediated endosomal
pathways, suggesting that Ad-HA/M-b-CyD has the potentials as a
tumor-selective antitumor agent.
Cutting-edge contributions from invited
poster presenters providing
significant research works in the third
International Symposium for
Medicinal Sciences (ISMS) in the 137th
Sendai annual meeting in 2017 are
assembled for the Current Topics section in
this issue of the Chemical and
Aggregation of amyloid β-peptide (Aβ) is closely linked to several neurodegeneration diseases including Alzheimer’s disease. Molecular dynamics simulations were performed to clarify the initial stage of Aβs interaction on the lipid membrane that mimicked a micro-domain on the neuronal cell surface. Stable complexes of Aβ peptides were not rapidly generated in simulation, instead a binding of two Aβs was gradually developed. In a stable two Aβs complex, one is bound to the membrane surface, while the other is attached to the first one without strong contact with membrane. A parallel β-sheet structure is formed between the C-terminal sides of them.