Structure-activity relationships study of -ethylene glycol-comprising alkyl heterocyclic carboxamides against A549 lung cancer cells.

Certain cancer cells depend on oxidative phosphorylation for survival; thus, inhibiting this process may be a promising treatment strategy. This study explored the structure-activity relationships of the mitochondrial inhibitor -ethylene glycol-comprising alkyl thiophene-3-carboxamide . We synthesized and evaluated 13 analogs (-) with different ethylene glycol units, heterocycles and connecting groups for their growth-inhibitory effects on A549 non-small cell lung cancer cells.

Ammonium carboxylates in the ammonia-Ugi reaction: one-pot synthesis of α,α-disubstituted amino acid derivatives including unnatural dipeptides.

Despite the remarkable developments of the Ugi reaction and its variants, the use of ammonia in the Ugi reaction has long been recognized as impractical and unsuccessful. Indeed, the ammonia-Ugi reaction often requires harsh reaction conditions, such as heating and microwave irradiation, and competes with the Passerini reaction, thereby resulting in low yields. This study describes a robust and practical ammonia-Ugi reaction protocol.

Phylogeographic History of Endangered Hokuriku Salamander, (Amphibia: Caudata).

Knowledge of the phylogeographic history of organisms is valuable for understanding their evolutionary processes. To the best of our knowledge, the phylogeographic structure of Hokuriku salamander, , an endangered species, remains unclear. This study aimed to elucidate the phylogeographic history of , which is expected to be strongly influenced by paleogeographic events.

Ring expansion of spirocyclopropanes with stabilized sulfonium ylides: highly diastereoselective synthesis of cyclobutanes.

A novel method was devised for regioselective ring expansion of Meldrum's acid-derived spirocyclopropanes to spirocyclobutanes with stabilized sulfonium ylides, affording 1,2--disubstituted 6,8-dioxaspiro[3.5]nonane-5,9-diones in up to 87% yields without the formation of any isomers. The aforementioned reaction was also applied to the barbituric acid-derived spirocyclopropane, resulting in the formation of the corresponding cyclobutanes.

8-Iodoisoquinolinone, a Conformationally Rigid Highly Reactive 2-Iodobenzamide Catalyst for the Oxidation of Alcohols by Hypervalent Iodine.

The first lactam-type 2-iodobenzamide catalysts, 8-iodoisoquinolinones 8 (IB-lactam) and 9 (MeO-IB-lactam), were developed. These catalysts have a conformationally rigid 6/6 bicyclic lactam structure and are more reactive than the previously reported catalysts 2-iodobenzamides 4 (IBamide) and 5 (MeO-IBamide) for the oxidation of alcohols. The lactam structure could form an efficient intramolecular I---O interaction, depending on the size of the lactam ring.

A SmI-mediated reductive cyclisation reaction using the trifluoroacetamide group as the radical precursor.

A samarium(II)-mediated reductive cyclisation reaction with the aminoketyl radical from the trifluoroacetamide group for synthesising 2-trifluoromethylindolines was developed. This reaction is the first example of using an acyclic amide group, which is considered difficult to react with SmI, in a reductive cyclisation. Additionally, the conversion of the obtained product into 2-trifluoromethylindole was achieved.

Efficient and Environmentally Benign Oxidative Cleavage of Pyrrolidine-2-methanols to γ-Lactams Using 2-Iodobenzamide as a Catalyst and Oxone.

The oxidative cleavage reaction of pyrrolidine-2-methanols to γ-lactams has been described. In this reaction, [4-iodo-3-(isopropylcarbamoyl)phenoxy]acetic acid and powdered Oxone (2KHSO·KHSO·KSO) were employed as the catalyst and co-oxidant, respectively. The reaction is efficient and environmentally benign because it produces various lactams from readily available substrates in moderate to excellent yields using organocatalyst and inorganic non-toxic co-oxidant.

Regioselective SmI-Mediated Radical ipso-Substitution Cyclization for the Construction of Pyrrolophenanthridinone Skeletons: The Synthesis of Amaryllidaceae Alkaloids.

Here, we report a regioselective, samarium(II) diiodide mediated intramolecular radical ipso-substitution cyclization. Through the use of a methoxy group as a leaving group, it was possible to regulate the regioselectivity of the reaction by changing the temperature and additives. We applied the developed reaction to the synthesis of four Amaryllidaceae alkaloids and have shown that the present reaction successfully overcomes regioselectivity issues encountered with other cyclization methods.

Thiophene Carboxamide Analogs with Long Alkyl Chains Comprising Ethylene Glycol Units Inhibit Glioblastoma Cell Proliferation by Activating AMPK.

Glioblastoma is a refractory malignant tumor that requires novel therapeutic strategies for effective treatment. We have previously reported that JCI-20679 (), an analog of annonaceous acetogenins, shows potent antitumor activity against glioblastomas. However, the synthesis of requires 23 steps, including 16 steps for the preparation of a tetrahydrofuran (THF) moiety.

Volumetric Modulated Arc Therapy Planning for Craniospinal Irradiation With a New O-ring Linac.

This study aims to determine the feasibility of using a new O-ring linear accelerator (Halcyon, Varian Medical Systems, CA, USA) to perform treatment planning using volumetric modulated arc therapy (VMAT) for craniospinal irradiation (CSI). A 20-year-old male patient with leukemia was selected. The planning target volume (PTV) was contoured to include the entire contents of the brain and spinal canal.

Synthesis of Acetogenin Analogs Comprising Pyrimidine Moieties Linked by Amine Bonds and Their Inhibitory Activity against Human Cancer Cell Lines.

Here, we synthesized three acetogenin analogs containing pyrimidine moieties linked by amine bonds, which represent the skeleton structure of pyrimidifen, a mitochondrial complex I-inhibiting insecticide. Replacing the pyrimidine moiety linked by the amine bond remarkably enhanced growth-inhibitory activity of the analogs against several human cancer cell lines. Moreover, these analogs selectively and potently inhibited the growth of these human cancer cell lines regardless of the pyrimidine substituents.

Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure.

Heart failure (HF) is a leading cause of death and repeated hospitalizations and often involves cardiac mitochondrial dysfunction. However, the underlying mechanisms largely remain elusive. Here, using a mouse model in which myocardial infarction (MI) was induced by coronary artery ligation, we show the metabolic basis of mitochondrial dysfunction in chronic HF.

Orbital angular momentum-resolved convergent-beam electron diffraction by the post-selected injection of electron beam.

Recent advances in the production of electron vortex beams carrying orbital angular momentum (OAM) offer unique opportunities to explore materials at the nanoscale level. We present a novel method for observing convergent-beam electron diffraction (CBED) patterns by using an electron vortex beam. In a transmission electron microscope, a series of electron vortex beams generated by a forked grating mask located above the specimen illuminate the specimen, and CBED patterns are imaged onto the observation plane of the microscope, selecting one of the electron vortex beams using an aperture located beneath the specimen.

Hybridization of Two Species of Japanese Toads, and , in the Central Part of Japan.

Interspecific hybridization between two species of Japanese toads, (Bt) and (Bjf), was not thought to have occurred due to the differences in their spawning habitats, although their hybridization was reported by previous research in a limited area. Such hybridization could have pivotal effects, such as genetic admixture, on Bt, which has a limited distribution and habitat. In this study, to clarify the details of hybridization, a total of 192 individuals were collected from multiple parapatric regions and an only Bjf allopatric region and analyzed based on morphology, mtDNA sequences, and nuclear DNA microsatellite loci.

Angiotensin-converting enzyme inhibitor prevents skeletal muscle fibrosis in diabetic mice.

New Findings: What is the central question of this study? We questioned whether an angiotensin-converting enzyme (ACE) inhibitor prevents skeletal muscle fibrosis in diabetic mice. What is the main finding and its importance? Administration of ACE inhibitor prevents the increase in skeletal muscle fibrosis during the early phase after induction of diabetes by streptozotocin. Our findings might provide a new therapeutic target for skeletal muscle abnormalities in diabetes.

Premedication with pioglitazone prevents doxorubicin-induced left ventricular dysfunction in mice.

Background: Doxorubicin (DOX) is widely used as an effective chemotherapeutic agent for cancers; however, DOX induces cardiac toxicity, called DOX-induced cardiomyopathy. Although DOX-induced cardiomyopathy is known to be associated with a high cumulative dose of DOX, the mechanisms of its long-term effects have not been completely elucidated. Pioglitazone (Pio) is presently contraindicated in patients with symptomatic heart failure owing to the side effects.

Brain-Derived Neurotrophic Factor Improves Impaired Fatty Acid Oxidation Via the Activation of Adenosine Monophosphate-Activated Protein Kinase-ɑ - Proliferator-Activated Receptor-r Coactivator-1ɑ Signaling in Skeletal Muscle of Mice With Heart Failure.

Background: We recently reported that treatment with rhBDNF (recombinant human brain-derived neurotrophic factor) improved the reduced exercise capacity of mice with heart failure (HF) after myocardial infarction (MI). Since BDNF is reported to enhance fatty acid oxidation, we herein conducted an in vivo investigation to determine whether the improvement in exercise capacity is due to the enhancement of the fatty acid oxidation of skeletal muscle via the AMPKα-PGC1α (adenosine monophosphate-activated protein kinase-ɑ-proliferator-activated receptor-r coactivator-1ɑ) axis.

Methods: MI and sham operations were conducted in C57BL/6J mice.

Type 2 diabetes is an independent predictor of lowered peak aerobic capacity in heart failure patients with non-reduced or reduced left ventricular ejection fraction.

Background: Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients' peak aerobic capacity.

Methods: We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF < 40%) who underwent cardiopulmonary exercise testing.

Mosquito repellence induced by tarsal contact with hydrophobic liquids.

Mosquito legs have a unique highly water-repellent surface structure. While being beneficial to mosquitoes, the water-repellence of the tarsi enhances the wettability of hydrophobic substances such as oils. This high wettability induces strong attraction forces on a mosquito's legs (up to 87% of the mosquito's weight) towards the oil.

Diacylglycerol acyltransferase 1/2 inhibition induces dysregulation of fatty acid metabolism and leads to intestinal barrier failure and diarrhea in mice.

The intestinal metabolism and transport of triacylglycerol (TAG) play a critical role in dietary TAG absorption, and defects in the process are associated with congenital diarrhea. The final reaction in TAG synthesis is catalyzed by diacylglycerol acyltransferase (DGAT1 and DGAT2), which uses activated fatty acids (FA) as substrates. Loss-of-function mutations in DGAT1 cause watery diarrhea in humans, but mechanisms underlying the relationship between altered DGAT activity and diarrhea remain largely unclear.

Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance.

Aims: Exercise intolerance in patients with heart failure (HF) is partly attributed to skeletal muscle abnormalities. We have shown that reactive oxygen species (ROS) play a crucial role in skeletal muscle abnormalities, but the pathogenic mechanism remains unclear. Xanthine oxidase (XO) is reported to be an important mediator of ROS overproduction in ischaemic tissue.

Ring-Opening Cyclization of Spirocyclopropanes Using Sulfoxonium Ylides.

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.

Angiotensin-converting-enzyme inhibitor prevents skeletal muscle fibrosis in myocardial infarction mice.

Background: Transforming growth factor beta (TGF-β)-Smad2/3 is the major signaling pathway of fibrosis, which is characterized by the excessive production and accumulation of extracellular matrix (ECM) components, including collagen. Although the ECM is an essential component of skeletal muscle, fibrosis may be harmful to muscle function. On the other hand, our previous studies have shown that levels of angiotensin II, which acts upstream of TGF-β-Smad2/3 signaling, is increased in mice with myocardial infarction (MI).

Protecting-Group-Free Formal Synthesis of Aspidospermidine: Ring-Opening Cyclization of Spirocyclopropane with Amine Followed by Regioselective Alkylations.

A concise formal synthesis of (±)-aspidospermidine via Stork's intermediate, which could be used as a divergent synthesis of alkaloids, was achieved by employing a ring-opening cyclization of spirocyclopropane with amine followed by a regioselective intramolecular/intermolecular alkylation sequence. Stork's intermediate was synthesized in only six steps from a simple starting material, 1,3-cyclohexanedione, and was converted into (±)-aspidospermidine. To the best of our knowledge, this synthesis of Stork's intermediate involves the least number of steps to date.

Empagliflozin restores lowered exercise endurance capacity via the activation of skeletal muscle fatty acid oxidation in a murine model of heart failure.

Decreased exercise capacity, which is an independent predictor of the poor prognosis of patients with heart failure (HF), is attributed to markedly impaired skeletal muscle mitochondrial function and fatty acid oxidation. Previous studies reported that the administration of an inhibitor of sodium-glucose cotransporter 2 (SGLT2) increases ketone body production and fat utilization in type 2 diabetic mice. In this study, we investigated the effects of SGLT2 inhibitor administration on exercise endurance and skeletal muscle mitochondrial function with fatty acid oxidation in a murine model of HF after the induction of myocardial infarction (MI).