Tag: M.W=100-150

Wang, Shuo published the artcileStructure-activity relationship study of dihydroartemisinin C-10 hemiacetal derivatives as Toll-like receptor 4 antagonists, Formula: C5H12O2, the publication is Bioorganic Chemistry (2021), 105107, database is CAplus and MEDLINE.

Dihydroartemisinin (DHA), a natural product isolated from the traditional Chinese herb Artemisia annua and one of the clin. frontline drugs against malarial infections, has recently been discovered as a Toll-like Receptor 4 (TLR4) antagonist. However, the TLR4 antagonistic activity of DHA is modest and it exhibits cellular toxicity. In this work, the structure-activity relationship (SAR) of DHA as TLR4 antagonist was explored. Since destroying the sesquiterpene endoperoxide scaffold substantially compromised the TLR4 antagonistic activity and mol. dynamics anal. showed that the C-10 hydroxyl group formed a hydrogen bond with E72 of myeloid differentiation factor 2 (MD2) to prevent it moving deeper into MD2, SAR of DHA was focused on the C-10 hemiacetal position. With extending the length of the linear alkane chain at C10 position, the TLR4 antagonistic activity of DHA analogs increased first and then decreased with the best TLR4 antagonism occurring at the length of the carbon chain of 3-4 carbons. In contrast, the cellular toxicity of DHA analogs was raised with the increasing length of the linear alkane chain. The TLR4 antagonistic activity of DHA derivatives with substituted halogen as the terminal functional group decreased with the decrease of electronegativity of the substituted halogen, which implies the electron-rich functional group at the end of the alkane chain appears preferred. Therefore, DHA derivative 2k with alkynyl as the end functional group, exhibited 14 times more potent TLR4 antagonistic activity than DHA. Moreover, 2k showed less cellular toxicity than DHA. Cellular signaling characterizations indicated that 2k inhibited LPS-induced TLR4 dimerization and endocytosis and suppressed LPS-induced NF-κB but not MAPKs activation, culminating in blocking LPS-induced TLR4 signaling downstream pro-inflammatory factors NO and IL-1β. Further, 2k was active in vivo; it significantly increased and prolonged morphine analgesia. Collectively, this study provides a structural guidance to reposition DHA derivatives as TLR4 antagonists.

Bioorganic Chemistry published new progress about 111-29-5. 111-29-5 belongs to alcohols-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Alcohol,Ploymers, name is Pentane-1,5-diol, and the molecular formula is C12H20O6, Formula: C5H12O2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Yuan, Bin published the artcileActivatable Photosensitizer for Smart Photodynamic Therapy Triggered by Reactive Oxygen Species in Tumor Cells, Recommanded Product: 4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-ol, the publication is ACS Applied Materials & Interfaces (2020), 12(24), 26982-26990, database is CAplus and MEDLINE.

Photodynamic therapy (PDT) is a promising approach for the treatment of different kinds of cancers as well as some other diseases. By combining spatiotemporal light irradiation with photosensitizers (PS), PDT can be easily controlled by tuning illumination time and sites of irradiation However, how to reduce the phototoxicity of the PS to normal cells without sacrificing its effectiveness to cancer cells is still a challenge. Herein, we put forward a deactivation and reactivation strategy for PDT to reduce the undesired damage to normal cells under light irradiation First, by chem. modification of meso-(4-pyridinyl)-substitution BODIPY with phenylboronic acid pinacol ester moiety, the masked PS ProBODIPY-2I with low generation efficiency of singlet oxygen and good water solubility can be obtained. Moreover, ProBODIPY-2I can be reactivated at tumor microenvironment by reactive oxygen species (ROS), resuming their PDT efficiency. Meanwhile, ProBODIPY-2I showed low phototoxicity for the normal cells, due to the relatively low concentration of ROS. In this way, the safety and selectivity for the PDT can be greatly improved. It is anticipated that some other tumor biomarkers, such as proton, GSH and enzymes, can be employed for the smart PDT methods.

ACS Applied Materials & Interfaces published new progress about 25240-59-9. 25240-59-9 belongs to alcohols-buliding-blocks, auxiliary class Boronic acid and ester,Boronic Acids,Boronate Esters, name is 4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-ol, and the molecular formula is C17H20ClN3, Recommanded Product: 4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-ol.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Zheng, Sheng published the artcileProdrug polymeric micelles integrating cancer-associated fibroblasts deactivation and synergistic chemotherapy for gastric cancer, HPLC of Formula: 4410-99-5, the publication is Journal of Nanobiotechnology (2021), 19(1), 381, database is CAplus and MEDLINE.

The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC.

Journal of Nanobiotechnology published new progress about 4410-99-5. 4410-99-5 belongs to alcohols-buliding-blocks, auxiliary class Thiol,Benzene, name is 2-Phenylethanethiol, and the molecular formula is C9H4F6O, HPLC of Formula: 4410-99-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Hu, Guilin published the artcileEffect of roasting degree of coffee beans on sensory evaluation: Research from the perspective of major chemical ingredients, COA of Formula: C4H6O5, the main research area is roasting coffee beans; Chemical ingredients; Cluster heatmap; Multivariate analysis; Roasted coffee beans; Sensory indicator; Sensory molecular network.

As the most consumed beverage in the world, the material basis of the sensory quality for roasted coffee beans has always received much attention. The objective of the present study was to clarify the phys. morphol. changes, main chem. ingredients and cupping scores of arabica coffee beans of different roasting degrees, by SEM (SEM), NMR (NMR) and sensory anal., resp. Statistical anal. of the data by multivariate anal. demonstrated that trigonelline, sugars, malate, quinic acids, γ-butyro-lactone and acetate have the potential to be new roasting markers. Addnl., in all the sensory indicators, body and acidity were found to be susceptible to roasting degree. Basing on cluster heatmap and sensory mol. network, the complex relationships between sensory indicators and ingredients were discussed. The results of partial least squares regression (PLSR) showed that the content of the main coffee ingredients can be used to predict the body score.

Food Chemistry published new progress about Boiling point. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, COA of Formula: C4H6O5.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Zhang, Yao published the artcileIDH2 compensates for IDH1 mutation to maintain cell survival under hypoxic conditions in IDH1-mutant tumor cells, Category: alcohols-buliding-blocks, the main research area is mutation cell survival proliferation glioma colon cancer.

Mutations of isocitrate dehydrogenase (IDH) 1 and 2 occur in low-grade gliomas, acute myeloid leukemias and other types of solid cancer. By catalyzing the reversible conversion between isocitrate and α-ketoglutarate (α-KG), IDH1 and 2 contribute to the central process of metabolism, including oxidative and reductive metabolism IDH1 and 2 mutations result in the loss of normal catalytic function and acquire neomorphic activity, facilitating the conversion of α-KG into an oncometabolite, (R)-2-hydroxyglutarate, which can cause epigenetic modifications and tumorigenesis. Small-mol. inhibitors of mutant IDH1 and 2 have been developed, and ongoing clin. trials have shown promising results in hematol. malignancies, but not in gliomas. These previous findings make it necessary to identify the mechanism and develop more effective therapies for IDH1-mutant gliomas. In the present study, it was demonstrated that under hypoxic conditions, patient-derived primary glioma cells and HCT116 cells, both of which carry a monoallelic IDH1 arginine 132 to histidine mutation (R132H), have a slower growth rate than the corresponding wild-type IDH1 cells. Western blot anal. showed that IDH1 R132H-mutant cancer cells exhibited upregulated IDH2 protein expression under hypoxic conditions. Furthermore, the silencing of IDH2 using small interfering RNA significantly inhibited the growth of IDH1-mutant cells under hypoxic conditions. Finally, [U-13C5]glutamine tracer anal. showed that IDH2 knockdown reduced the reductive carboxylation of α-KG into isocitrate in HCT116R132H/+ cells under hypoxic conditions. The present study showed for the first time, to the best of our knowledge, that IDH2 plays a compensatory role in maintaining reductive carboxylation-dependent lipogenesis and proliferation in IDH1 R132H tumor cells. Therefore, IDH2 could serve as a potential anti-tumor target for IDH1-mutant tumors, which may provide a new strategy for treatment.

Molecular Medicine Reports published new progress about Carboxylation. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Category: alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

DiMario, Robert J. published the artcileA single serine to alanine substitution decreases bicarbonate affinity of phosphoenolpyruvate carboxylase in C4Flaveria trinervia, Safety of (S)-2-hydroxysuccinic acid, the main research area is Flaveria phosphoenolpyruvate carboxylase bicarbonate affinity substitution.

Phosphoenolpyruvate (PEP) carboxylase (PEPc) catalyzes the first committed step of C4 photosynthesis generating oxaloacetate from bicarbonate (HCO3-) and PEP. It is hypothesized that PEPc affinity for HCO3- has undergone selective pressure for a lower KHCO3 (Km for HCO3-) to increase the carbon flux entering the C4 cycle, particularly during conditions that limit CO2 availability. However, the decrease in KHCO3 has been hypothesized to cause an unavoidable increase in KPEP (Km for PEP). Therefore, the amino acid residue S774 in the C4 enzyme, which has been shown to increase KPEP, should lead to a decrease in KHCO3. Several studies reported the effect S774 has on KPEP; however, the influence of this amino acid substitution on KHCO3 has not been tested. To test these hypotheses, membrane-inlet mass spectrometry (MIMS) was used to measure the KHCO3 of the photosynthetic PEPc from the C4Flaveria trinervia and the non-photosynthetic PEPc from the C3 F. pringlei. The cDNAs for these enzymes were overexpressed and purified from the PEPc-less PCR1 Escherichia coli strain. Our work in comparison with previous reports suggests that KHCO3 and KPEP are linked by specific amino acids, such as S774; however, these kinetic parameters respond differently to the tested allosteric regulators, malate and glucose-6-phosphate.

Journal of Experimental Botany published new progress about Carboxylation. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Safety of (S)-2-hydroxysuccinic acid.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Wang, Wenying published the artcileHemichannel-mediated volume regulation contributes to IPC-induced cardiomyocyte protection, Related Products of alcohols-buliding-blocks, the main research area is IPC cardiomyocyte protection hemichannel mediated volume regulation contribute; capacity regulation; hemichannels; ischemic preconditioning; myocardial protection.

Cx43 has been documented to be involved in ischemic preconditioning (IPC). However, the participation of Cx43-formed hemichannels in IPC and the potential underlying mechanisms remain unclear. The present study focused on cardiomyocytes’ volume regulation during IPC to investigate the role of hemichannels in the IPC-induced cardioprotection. In the study, mice cardiomyocytes were resp. treated with a hemichannel blocker, octanol or 18a-Glycyrrhizic acid (18a-GA), and a Cx43-silenced lentivirus. They were subsequently cultured in hypotonic solution to simulate ischemic reperfusion (SIR) and systemic ischemic preconditioning (SIP). Cell morphol. and volumetric (area) change were detected by inverted microscopy at 30 min following the addition of hypotonic solution Cardiomyocyte mortality was assessed by trypan blue stain assay. The analyses revealed that regardless of the treatments, hypotonic solution aggravated cell edema: Compared with the initial condition (the moment before the solution addition, 0 min), the volumetric area increased significantly 30 min later (for hypotonic + DMSO, 5,050 ± 1,511 vs. 3,464 ± 723μm2; for hypotonic+scramble lentiviral vector, 5,517 ± 1,128 vs. 2,331 ± 536μm2; P<0.05, resp.). Either treatment alleviated the edematous condition when a comparison was made between 30 min after the hypotonic addition and 0 min (for hypotonic+octanol, 2,990 ± 765 vs. 2,821 ± 773μm2; for hypotonic+18a-GA, 4,817 ± 1,306 vs. 4,762 ± 1,271μm2; for hypotonic + Cx43-silenced, 3,627 ± 688 vs. 3,419 ± 814μm2; P>0.05 for all). Notably, results indicated that the SIP group had lower mortality rates compared with its SIR counterpart; the hypotonic + octanol, hypotonic + 18a-GA, and hypotonic + Cx43-silenced group showed markedly-declined mortality when compared with their resp. control groups (resp., 35.70 ± 1.02, 30.76 ± 2.20 vs. 53.58 ± 2.14%; 30.89 ± 2.37 vs. 54.12 ± 2.55%; P<0.05 for all). The results suggest that ischemic preconditioning may provide cardioprotection by blocking the opening of the hemichannels and further mediating the volume regulation of cardiomyocytes. Experimental and Therapeutic Medicine published new progress about Cardiomyocyte. 111-87-5 belongs to class alcohols-buliding-blocks, name is n-Octanol, and the molecular formula is C8H18O, Related Products of alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Colin, Camille published the artcileSingle-particle tracking method in fluorescence microscopy to monitor bioenergetic responses of individual mitochondria, Related Products of alcohols-buliding-blocks, the main research area is single particle tracking mitochondrial permeability transition pore fluorescence microscopy; Bioenergetics; Fiji software; Fluorescence microscopy; Membrane potential; Mitochondria; Single organelle; Single particle tracking; TrackMate.

The spectroscopic methods commonly used to study mitochondria bioenergetics do not show the diversity of responses within a population of mitochondria (isolated or in a cell), and/or cannot measure individual dynamics. New methodol. developments are necessary in order to improve quant. and kinetic resolutions and eventually gain further insights on individual mitochondrial responses, such as studying activities of the mitochondrial permeability transition pore (mPTP). The work reported herein is devoted to study responses of single mitochondria within a large population after isolation from cardiomyocytes. Mitochondria were preloaded with a commonly used membrane potential sensitive dye (TMRM), they are then deposited on a plasma-treated glass coverslip and subsequently energized or inhibited by additions of usual bioenergetics effectors. Responses were analyzed by fluorescence microscopy over few thousands of mitochondria simultaneously with a single organelle resolution We report an automatic method to analyze each image of time-lapse stacks based on the TrackMate-ImageJ plug-in and specially made Python scripts. Images are processed to eliminate defects of illumination inhomogeneity, improving by at least two orders of magnitude the signal/noise ratio. This method enables us to follow the track of each mitochondrion within the observed field and monitor its fluorescence changes, with a time resolution of 400 ms, uninterrupted over the course of the experiment Such methodol. improvement is a prerequisite to further study the role of mPTP in single mitochondria during calcium transient loading.

Methods in Molecular Biology (New York, NY, United States) published new progress about Cardiomyocyte. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Related Products of alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Yu, Peng published the artcileTemperature dependence of mitoflash biogenesis in cardiac mitochondria, Related Products of alcohols-buliding-blocks, the main research area is mitochondrial mitoflash cardiomyocyte temperature.

Mitochondrial flashes represent fundamental biochem. and biophys. dynamics of the organelle, involving sudden depolarization of mitochondrial membrane potential (ΔΨm), bursting production of ROS, and accelerated extrusion of matrix protons. Here we investigated temperature dependence of mitoflash biogenesis as well as ΔΨm oscillations, a subset of which overlapping with mitoflashes, in both cardiac myocytes and cardiac mitochondria. Unexpectedly, we found that mitoflash biogenesis was essentially temperature-independent in intact cardiac myocytes, evidenced by the constancy of frequency as well as amplitude and rise speed over 5°C-40°C. Moderate temperature dependence was found in single mitochondria charged by respiratory substrates, where mitoflash frequency was decreased over 5°C-20°C with Q10 of 0.74 for Complex I substrates and 0.83 for Complex II substrate. In contrast, ΔΨm oscillation frequency displayed a neg. temperature dependence at 5°C-20°C with Q10 of 0.82 in intact cells, but a pos. temperature dependence at 25°C – 40°C with Q10 of 1.62 in isolated mitochondria charged with either Complex I or Complex II substrates. These results suggest a temperature compensation of mitoflash frequency at both the mitochondrial and extra-organelle levels, and underscore that mitoflashes and ΔΨm oscillations are related but distinctly different mitochondrial functional dynamics.

Archives of Biochemistry and Biophysics published new progress about Cardiomyocyte. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Related Products of alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Li, Qing published the artcileCircular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR-338-3p/PKM2 Axis Under Hypoxic Stress, SDS of cas: 97-67-6, the main research area is RNA MATB glycolysis malignancy hepatocellular carcinoma PKM prognosis stress.

Glucose metabolism reprogramming, which is a well-established characteristic of multiple cancers, demands a higher rate of glycolysis to meet the increasing demands for macromol. synthesis and to maintain rapid proliferation in a hypoxic environment. However, the mechanism underlying this switch remains to be elucidated. In this study, we investigated the function of circular RNA MAT2B (circMAT2B) in hepatocellular carcinoma (HCC) glucose metabolism reprogramming and malignancy. CircMAT2B was identified by bioinformatics anal. of Gene Expression Omnibus data sets. CircMAT2B expression was up-regulated in HCC tissues and cell lines. HCC patients with high circMAT2B expression had shortened overall survival. We analyzed the pos. correlation between glycolysis and circMAT2B expression in HCC using a maximum standardized uptake value determined by preoperative positron emission tomog./computed tomog. scanning combined with high-performance liquid chromatog. assessment of the metabolites of glycolysis and the citric acid cycle. The effect of circMAT2B on glycolysis was validated in vitro and in vivo under hypoxic (1% O2) conditions. Functional assays were performed in HCC cells, HCC organoids, and nude mice to explore the tumor-promoting roles of circMAT2B in HCC. Biotin-coupled probe pull-down assays, biotin-coupled microRNA capture, luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation assays were performed to confirm the interaction among different RNAs. Mechanistically, we demonstrated that circMAT2B up-regulated expression levels of the microRNA (miR)-338-3p target gene PKM2, which encodes a key enzyme in the process of glycolysis, through “”sponging”” miR-338-3p; thus, glycolysis and HCC progression are promoted through this mechanism. Conclusion: CircMAT2B promoted HCC progression by enhanced glycolysis by activating the circMAT2B/miR-338-3p/PKM2 axis under hypoxia, which may provide a therapeutic target for HCC.

Hepatology (Hoboken, NJ, United States) published new progress about Cell invasion. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, SDS of cas: 97-67-6.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts