13,434 results match your criteria Bioorganic & Medicinal Chemistry[Journal]


Homopurine R-stereodefined phosphorothioate analogs of DNA with hampered Watson-Crick base pairings form Hoogsteen paired parallel duplexes with (2'-OMe)-RNAs.

Org Biomol Chem 2019 Apr 24. Epub 2019 Apr 24.

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Łódź, Poland.

3'-O-(2-Thio-4,4-pentamethylene-1,3,2-oxathiaphospholane) derivatives of 5'-O-DMT-N6-methyl-deoxyadenosine and 5'-O-DMT-N2,N2-dimethyl-O6-diphenylcarbamoyl-deoxyguanosine (OTP-NY, NY = DMT-m6dA or DMT-m,m2dGDPC) were synthesized, resolved onto pure P-diastereomers, and used in P-stereocontrolled synthesis of dinucleoside 3',5,-phosphorothioates NXPST (NX = m6dA or m,m2dG), in which the absolute configuration of the stereogenic phosphorus atom was established enzymatically. Diastereomerically pure OTP-NY and standard OTP-N (N = DMT-dABz or DMT-dGBz,DPC) were used in the synthesis of chimeric RP-stereodefined phosphorothioate oligomers ((RP-PS)-DN(NX)A) with hampered Watson-Crick base pairings. It was found that the m6dA units slightly reduce the thermodynamic stability of antiparallel duplexes formed with RNA and (2'-OMe)-RNA matrices, whereas m,m2dG units prevent their formation. Read More

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http://dx.doi.org/10.1039/c8ob03112fDOI Listing

The Prospect of Photochemical Reactions in Confined Gel Media.

Acc Chem Res 2019 Apr 24. Epub 2019 Apr 24.

Institut für Organische Chemie , Universität Regensburg , Universitätsstr. 31 , 93053 Regensburg , Germany.

Nature is intrinsically able to control kinetics, conversion, and selectivity of biochemical processes by means of confined reaction environments such as enzyme pockets, bilayer membranes, micelles, vesicles, cells, or bioorganic frameworks. The main reason for this fact is the optimal molecular alignment and restricted motion of reactant molecules compared to those found in bulk solution. Under this inspiration, a number of synthetic photo-nanoreactors based on supramolecular self-assembled systems have been developed during the last decades, including mesoporous inorganic materials, microemulsions, micelles, vesicles, lipid bilayer foams, polyelectrolyte nanoparticles, etc. Read More

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http://dx.doi.org/10.1021/acs.accounts.9b00097DOI Listing

Oligonucleotide Primers with G-Clamp Modifications for RT-qPCR Detection of the Low-Copy dsRNA.

Methods Mol Biol 2019 ;1973:281-297

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

We developed a new technique suitable for improved detection of low-copy dsRNA using modified oligonucleotides as primers in RT-qPCR. Insertion of G-clamp residues into primers significantly improves thermal stability of duplexes with RNA without decrease of hybridization selectivity. The applicability of modified primers is demonstrated for detection of low-copy Kemerovo virus dsRNA. Read More

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http://dx.doi.org/10.1007/978-1-4939-9216-4_18DOI Listing
January 2019

Synthesis and Enzymatic Characterization of Sugar-Modified Nucleoside Triphosphate Analogs.

Methods Mol Biol 2019 ;1973:1-13

Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, CNRS UMR 3523, Institut Pasteur, Paris, France.

Chemical modification of nucleic acids can be achieved by the enzymatic polymerization of modified nucleoside triphosphates (dN*TPs). This approach obviates some of the requirements and drawbacks imposed by the more traditional solid-phase synthesis of oligonucleotides. Here, we describe the protocol that is necessary to synthesize dN*TPs and evaluate their substrate acceptance by polymerases for their subsequent use in various applications including selection experiments to identify aptamers. Read More

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http://dx.doi.org/10.1007/978-1-4939-9216-4_1DOI Listing
January 2019
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Enhanced Proapoptotic Effects of Water Dispersed Complexes of 4-Thiazolidinone-Based Chemotherapeutics with a PEG-Containing Polymeric Nanocarrier.

Nanoscale Res Lett 2019 Apr 23;14(1):140. Epub 2019 Apr 23.

International Research and Innovation in Medicine Program, Cedars-Sinai Medical Center, Los Angeles, CA, 90048-5502, USA.

Aim: To study whether water formulation of the complex of 4-thiazolidinone derivatives with a PEG-containing polymeric nanocarrier enhances their pro-apoptotic action towards rat glioma C6 cells.

Methods: Mechanisms of antineoplastic effects of 4-thiazolidinone derivatives were investigated in vitro with rat glioma C6 cells. Cell nativity, cell cycling pattern, and Annexin V expression were evaluated and DNA damage was estimated by DNA comet analysis. Read More

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http://dx.doi.org/10.1186/s11671-019-2945-7DOI Listing

Thiosemicarbazones with tyrosinase inhibitory activity.

Medchemcomm 2019 Mar 5;10(3):378-389. Epub 2019 Feb 5.

Wrocław University of Science and Technology , Department of Bioorganic Chemistry , Wybrzeże Wyspiańskiego 27 , 50-370 , Wrocław , Poland . Email:

Tyrosinase plays an essential role in melanogenesis. Excess production of melanin can be a reason for hyperpigmentation skin disorders in mammals and enzymatic browning in plant-derived foods. Catalyzing the rate-limiting step of melanin synthesis, tyrosinase has become the most studied target for melanogenesis inhibition. Read More

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http://dx.doi.org/10.1039/c9md00005dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457196PMC

Semisynthetic aurones inhibit tubulin polymerization at the colchicine-binding site and repress PC-3 tumor xenografts in nude mice and myc-induced T-ALL in zebrafish.

Sci Rep 2019 Apr 23;9(1):6439. Epub 2019 Apr 23.

Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, 40536-0509, USA.

Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the leading, biologically active analogs were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5b) that inhibited in vitro PC-3 prostate cancer cell proliferation with IC values below 100 nM. A xenograft study in nude mice using 10 mg/kg of 5a had no effect on mice weight, and aurone 5a did not inhibit, as desired, the human ether-à-go-go-related (hERG) potassium channel. Read More

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http://dx.doi.org/10.1038/s41598-019-42917-0DOI Listing

Atlas of RNA sequencing profiles for normal human tissues.

Sci Data 2019 Apr 23;6(1):36. Epub 2019 Apr 23.

Omicsway Corp., 340S Lemon Ave, 6040, Walnut, 91789 CA, USA.

Comprehensive analysis of molecular pathology requires a collection of reference samples representing normal tissues from healthy donors. For the available limited collections of normal tissues from postmortal donors, there is a problem of data incompatibility, as different datasets generated using different experimental platforms often cannot be merged in a single panel. Here, we constructed and deposited the gene expression database of normal human tissues based on uniformly screened original sequencing data. Read More

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http://dx.doi.org/10.1038/s41597-019-0043-4DOI Listing
April 2019
1 Read

Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2.

Blood 2019 Apr 23. Epub 2019 Apr 23.

NIAMS/NIH, United States.

Reduction of adenosine deaminase 2 (ADA2) activity due to autosomal recessive loss-of-function mutations in the ADA2 gene (previously known as CECR1) results in a systemic vasculitis known as deficiency of ADA2 (DADA2). Neutrophils and a subset of neutrophils known as low-density granulocytes (LDGs) have been implicated in the pathogenesis of vasculitis, at least in part, through the formation of neutrophil extracellular traps (NETs). The study objective was to determine whether neutrophils and NETs play a pathogenic role in DADA2. Read More

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http://dx.doi.org/10.1182/blood.2018892752DOI Listing

Manufacture of Networks from Large Diameter Single-Walled Carbon Nanotubes of Particular Electrical Character.

Nanomaterials (Basel) 2019 Apr 14;9(4). Epub 2019 Apr 14.

Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.

We have demonstrated that the aqueous two-phase extraction (ATPE) can differentiate between large diameter single-walled carbon nanotubes (CNTs) by electrical character. Introduction of "hydration modulators" to the ATPE machinery has enabled us to isolate metallic and semiconducting CNTs with ease. We have also shown that often there is a trade-off between the purity of the obtained fractions and the ability to separate both metallic and semiconducting CNTs at the same time. Read More

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http://dx.doi.org/10.3390/nano9040614DOI Listing

Virus-Like Particle Facilitated Deposition of Hydroxyapatite Bone Mineral on Nanocellulose after Exposure to Phosphate and Calcium Precursors.

Int J Mol Sci 2019 Apr 12;20(8). Epub 2019 Apr 12.

Cell and Molecular Sciences, The James Hutton Institute, Dundee DD2 5DA, UK.

We produced and isolated tobacco mosaic virus-like particles (TMV VLPs) from bacteria, which are devoid of infectious genomes, and found that they have a net negative charge and can bind calcium ions. Moreover, we showed that the TMV VLPs could associate strongly with nanocellulose slurry after a simple mixing step. We sequentially exposed nanocellulose alone or slurries mixed with the TMV VLPs to calcium and phosphate salts and utilized physicochemical approaches to demonstrate that bone mineral (hydroxyapatite) was deposited only in nanocellulose mixed with the TMV VLPs. Read More

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http://dx.doi.org/10.3390/ijms20081814DOI Listing

High-Throughput Biochemical Fingerprinting of Oleaginous sp. Strains by Fourier Transform Infrared Spectroscopy (FT-IR) for Lipid and Carbohydrate Productions.

Molecules 2019 Apr 22;24(8). Epub 2019 Apr 22.

Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, Shandong, China.

The traditional biochemical methods for analyzing cellular composition of oleaginous microorganisms are time-consuming, polluting, and expensive. In the present study, an FT-IR method was used to analyze the cellular composition of the marine oleaginous protist sp. during various research processes, such as strains screening, medium optimization, and fermentation, and was evaluated as a green, low-cost, high throughput, and accurate method compared with the traditional methods. Read More

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http://dx.doi.org/10.3390/molecules24081593DOI Listing

Functional Analysis of Coilin in Virus Resistance and Stress Tolerance of Potato Solanum tuberosum using CRISPR-Cas9 Editing.

Dokl Biochem Biophys 2019 May 22;484(1):88-91. Epub 2019 Apr 22.

Doka Gene Technologies Ltd, 141880, Rogachevo, Moscow oblast, Russia.

The role of the nuclear protein coilin in the mechanisms of resistance of potato Solanum tuberosum cultivar Chicago to biotic and abiotic stresses was studied using the CRISPR-Cas9 technology. For the coilin gene editing, a complex consisting of the Cas9 endonuclease and a short guide RNA was immobilized on gold or chitosan microparticles and delivered into apical meristem cells by bioballistics or vacuum infiltration methods, respectively. Editing at least one allele of the coilin gene considerably increased the resistance of the edited lines to infection with the potato virus Y and their tolerance to salt and osmotic stress. Read More

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http://dx.doi.org/10.1134/S1607672919010241DOI Listing

Biotechnological Method of Preparation and Characterization of Recombinant Antimicrobial Peptide Avicin A from Enterococcus avium.

Dokl Biochem Biophys 2019 May 22;484(1):42-44. Epub 2019 Apr 22.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.

Avicin A is a bacteriocin from the gram-positive bacterium Enterococcus avium. It exhibits a high microbicidal activity against bacteria of the genus Listeria, a causative agent of the severe human infection listeriosis. We developed a biotechnological method for obtaining avicin A and characterized its structure and biological activity. Read More

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http://dx.doi.org/10.1134/S1607672919010113DOI Listing

Recombinant Production and Structure-Function Study of the Ts1 Toxin from the Brazilian Scorpion Tityus serrulatus.

Dokl Biochem Biophys 2019 May 22;484(1):9-12. Epub 2019 Apr 22.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.

An effective bacterial system for the production of β-toxin Ts1, the main component of the Brazilian scorpion Tityus serrulatus venom, was developed. Recombinant toxin and its N-labeled analogue were obtained via direct expression of synthetic gene in Escherichia coli with subsequent folding from the inclusion bodies. According to NMR spectroscopy data, the recombinant toxin is structured in an aqueous solution and contains a significant fraction of β-structure. Read More

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http://dx.doi.org/10.1134/S1607672919010034DOI Listing

Diversity of Harpin-Like Defense Peptides from Barnyard Grass (Echinochloa crusgalli L.) Seeds.

Dokl Biochem Biophys 2019 May 22;484(1):6-8. Epub 2019 Apr 22.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, 117997, Moscow, Russia.

The results of the study of the structure and function of harpin-like peptides (alpha-harpinins) of the EcAMP group from the barnyard grass (E. crusgalli) seeds and the possibility of their involvement in the innate immunity to biotic stresses are presented. Read More

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http://dx.doi.org/10.1134/S1607672919010022DOI Listing

study of 4-phosphorylated derivatives of 1,3-oxazole as inhibitors of fructose-1,6-bisphosphate aldolase II.

Heliyon 2019 Apr 10;5(4):e01462. Epub 2019 Apr 10.

Department of Medical and Biological Researches, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.

In this study, the synthesis, anti-Candida activity and molecular modeling of 4-phosphorylated derivatives of 1,3-oxazole as inhibitors of fructose-1,6-bisphosphate aldolase (FBA-II) are demonstrated and discussed. Significant similarity of the primary and secondary structure, binding sites and active sites of FBA-II and are established. FBA-II inhibitors contained 1,3-oxazole-4-phosphonates moiety are created by analogy to inhibitors FBA-II . Read More

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http://dx.doi.org/10.1016/j.heliyon.2019.e01462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460381PMC

Adenosine A3 receptor activation inhibits pronociceptive N-type Ca2+ currents and cell excitability in dorsal root ganglion neurons.

Pain 2019 05;160(5):1103-1118

Division of Pharmacology and Toxicology, Department of NEUROFARBA, University of Florence, Italy.

Recently, studies have focused on the antihyperalgesic activity of the A3 adenosine receptor (A3AR) in several chronic pain models, but the cellular and molecular basis of this effect is still unknown. Here, we investigated the expression and functional effects of A3AR on the excitability of small- to medium-sized, capsaicin-sensitive, dorsal root ganglion (DRG) neurons isolated from 3- to 4-week-old rats. Real-time quantitative polymerase chain reaction experiments and immunofluorescence analysis revealed A3AR expression in DRG neurons. Read More

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http://dx.doi.org/10.1097/j.pain.0000000000001488DOI Listing
May 2019
1 Read

Cytotoxic polyphenolic compounds from Lespedeza bicolor stem bark.

Fitoterapia 2019 Apr 17. Epub 2019 Apr 17.

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok, 690022, Russia.

Four new pterocarpans (6aR,11aR)-6a,11a-dihydrolespedezol A (2), (6aR,11aR)-2-isoprenyl-6a,11a-dihydrolespedezol A (3), (6aR,11aR,3'R)-6a,11a-dihydrolespedezol A (4), (6aR,11aR,3'S)-6a,11a-dihydrolespedezol A (5) and one new stilbenoid with 1,2-diketone fragment named bicoloketone (6) along with one previously known pterocarpen lespedezol A (1) have been isolated from Lespedeza bicolor stem bark using multistage column chromatography on polyamide and silica gel. The structures of the isolated polyphenolic compounds were determined by spectroscopic methods. The absolute configurations of 4 and 5 were determined by comparison of their electronic circular dichroism (ECD) spectra obtained experimentally and the spectra calculated using time-dependent density functional theory (TDDFT). Read More

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http://dx.doi.org/10.1016/j.fitote.2019.04.003DOI Listing
April 2019
2 Reads

Dual DNA topoisomerase 1 and tyrosyl-DNA phosphodiesterase 1 inhibition for improved anticancer activity.

Med Res Rev 2019 Apr 19. Epub 2019 Apr 19.

Laboratory of Bioorganic Chemistry of Enzymes, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that catalyzes the hydrolysis of the phosphodiester bond in the DNA-topoisomerase 1 (Top1) covalent complex and repairs some other 3'-end DNA adducts. Currently, Tdp1 functions as an important target in cancer drug design owing to its ability to break down various DNA adducts induced by chemotherapeutics. Tdp1 inhibitors may sensitize tumor cells to the action of Top1 poisons, thereby potentiating their effects. Read More

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http://dx.doi.org/10.1002/med.21587DOI Listing

Immobilization of recombinant Escherichia coli whole cells harboring xylose reductase and glucose dehydrogenase for xylitol production from xylose mother liquor.

Bioresour Technol 2019 Apr 13;285:121344. Epub 2019 Apr 13.

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China; Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, PR China.

In this study, recombinant E. coli BL21(DE3)/pCDFDuet-1-XR-GDH harboring xylose reductase (XR) and glucose dehydrogenase (GDH) were immobilized and applied for the production of xylitol from xylose mother liquor (XML). Various immobilization methods were screened and the cross-linking approach with diatomite and polyetherimide as the raw materials and glutaraldehyde as the cross-linking agent was the optimal one, and the recovery activity reached of 80. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09608524193056
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http://dx.doi.org/10.1016/j.biortech.2019.121344DOI Listing
April 2019
2 Reads

Matrix attachment regions as a tool to influence plant transgene expression.

3 Biotech 2019 May 12;9(5):176. Epub 2019 Apr 12.

Biotron, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Puschino, Russia.

The inclusion of special regulatory sequences known as matrix attachment regions (MARs) in transgene constructs has been suggested as a possible approach to stabilise the expression of foreign heterological genes. The present review provides a brief summary regarding the MARs that have been used in investigations studying their influence on plant transgene expression in different plants with different promoters and reporter genes, and the comparison of these investigations. Read More

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http://dx.doi.org/10.1007/s13205-019-1709-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461602PMC

Durable liquid-crystalline vitrimer actuators.

Chem Sci 2019 Mar 23;10(10):3025-3030. Epub 2019 Jan 23.

MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology , Department of Chemistry , Tsinghua University , Beijing 100084 , China . Email:

Vitrimer-based liquid-crystalline elastomers (LCEs) exhibit great advantages over the traditional LCEs due to their inherent processability to realize monodomain alignment and construction of LCE actuators with complex 3D structures in a robust way. Though exciting progress has been made, how to achieve a proper balance between processability and actuation durability/stability remains a big challenge. Here, we report a strategy to mitigate the conflict between processability and actuation stability by reducing the catalyst content in an epoxy/acid LCE vitrimer system. Read More

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http://xlink.rsc.org/?DOI=C8SC05358H
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http://dx.doi.org/10.1039/c8sc05358hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427948PMC
March 2019
2 Reads

Direct Functionalization of White Phosphorus to Cyclotetraphosphanes: Selective Formation of Four P-C Bonds.

J Am Chem Soc 2019 Apr 18. Epub 2019 Apr 18.

Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry , Peking University , Beijing 100871 , China.

Converting elemental white phosphorus directly into organophosphorus or polyphosphorus is meaningful, challenging and attractive. The ate-complexes of aluminacyclopentadienes 1a,b react with P to afford selectively the cyclotetraphosphanes 2a,b featuring four newly formed P-C bonds and a planar square cyclo-P ring. Density functional theory calculations show that the conversion of tetrahedral P to planar cyclo-P moiety undergoes through an unexpected 1,1- P-insertion/Diels-Alder reaction/isomerization cascade process. Read More

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http://pubs.acs.org/doi/10.1021/jacs.9b02628
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http://dx.doi.org/10.1021/jacs.9b02628DOI Listing
April 2019
1 Read

Domain Diversity and Polarization Switching in Amino Acid β-Glycine.

Materials (Basel) 2019 Apr 15;12(8). Epub 2019 Apr 15.

School of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620000, Russia.

Piezoelectric materials based on lead zirconate titanate are widely used in sensors and actuators. However, their application is limited because of high processing temperature, brittleness, lack of conformal deposition and, more importantly, intrinsic incompatibility with biological environments. Recent studies on bioorganic piezoelectrics have demonstrated their potential in these applications, essentially due to using the same building blocks as those used by nature. Read More

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https://www.mdpi.com/1996-1944/12/8/1223
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http://dx.doi.org/10.3390/ma12081223DOI Listing
April 2019
1 Read

Identification of novel imidazole flavonoids as potent and selective inhibitors of protein tyrosine phosphatase.

Bioorg Chem 2019 Apr 9;88:102900. Epub 2019 Apr 9.

Laboratory of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China.

A series of imidazole flavonoids as new type of protein tyrosine phosphatase inhibitors were synthesized and characterized. Most of them gave potent protein phosphatase 1B (PTP1B) inhibitory activities. Especially, compound 11a could effectively inhibit PTP1B with an IC value of 0. Read More

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http://dx.doi.org/10.1016/j.bioorg.2019.03.074DOI Listing

Last of the gem-Difluorocycloalkanes: Synthesis and Characterization of 2,2-Difluorocyclobutyl-Substituted Building Blocks.

J Org Chem 2019 Apr 24. Epub 2019 Apr 24.

Enamine Ltd. , Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.

An efficient approach to synthesis of previously unavailable 2-substituted difluorocyclobutane building blocks was developed and applied on a multigram scale. The key step of the synthetic sequence included deoxofluorination of O-protected 2-(hydroxylmethyl)cyclobutanone. Dissociation constants (p K) and log  P values for 2,2-difluorocyclobutaneamine and 2,2-difluorocyclobutanecarboxylic acid or their derivatives were measured and compared with the values obtained for the corresponding 3,3-difluorocyclobutane derivatives and nonfluorinated counterparts. Read More

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http://dx.doi.org/10.1021/acs.joc.9b00719DOI Listing
April 2019
1 Read

Stereoselective Pd-Catalyzed Decarboxylative Allylation: Assembly of Highly Functionalized Allylic Amines Bearing a Quaternary Center.

Org Lett 2019 Apr 16. Epub 2019 Apr 16.

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics , Peking University Shenzhen Graduate School , Shenzhen 518055 , China.

Here, we report a practical and reliable methodology to direct construction of tri- and tetrasubstituted olefins bearing an allylic amine, with the concomitant construction of the sterically congested quaternary stereocenter through stereoselective palladium-catalyzed cascade decarboxylation of vinyloxazolidinones. Read More

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http://pubs.acs.org/doi/10.1021/acs.orglett.9b00673
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http://dx.doi.org/10.1021/acs.orglett.9b00673DOI Listing
April 2019
1 Read

Direct intramolecular carbon(sp)-nitrogen(sp) reductive elimination from gold(iii).

Dalton Trans 2019 Apr 16. Epub 2019 Apr 16.

Department of Chemistry, University of Kentucky, 505 Rose Street, Lexington, Kentucky 40506, USA.

The reactivity of bidentate AuIII-Cl species, [(C^N)AuCl2], with a bisphosphine or carbon donor ligands results in reductive elimination. Combined experimental and computational investigations lead to the first evidence of a direct intramolecular C(sp2)-N(sp2) bond formation from a monomeric [(C^N)AuCl2] gold(iii) complex. We show that bidentate ligated Au(iii) systems bypass transmetallation to form C(sp2)-N(sp2) species and NHC-Au-Cl. Read More

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http://xlink.rsc.org/?DOI=C8DT05155K
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http://dx.doi.org/10.1039/c8dt05155kDOI Listing
April 2019
1 Read

Magnetically Hollow Pt Nanocages with Ultrathin Walls as a Highly Integrated Nanoreactor for Catalytic Transfer Hydrogenation Reaction.

Adv Sci (Weinh) 2019 Apr 7;6(7):1802132. Epub 2019 Feb 7.

Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education) Beijing Key Lab of Microanalytical Methods & Instrumentation Department of Chemistry Center for Synthetic and Systems Biology Tsinghua University Beijing 100084 P. R. China.

Fabricating efficient and stable nanocatalysts for chemoselective hydrogenation of nitroaromatics is highly desirable because the amines hold tremendous promise for the synthesis of nitrogen containing chemicals. Here, a highly reactive and stable porous carbon nitride encapsulated magnetically hollow platinum nanocage is developed with subnanometer thick walls (FeO@Pt@PCN) for this transformation. This well-controlled nanoreactor is prepared via the following procedures: the preparation of core template, the deposition of platinum nanocage with subnanometer thick walls, oxidative etching, and calcination. Read More

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http://dx.doi.org/10.1002/advs.201802132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446610PMC

Nickel-catalysed selective migratory hydrothiolation of alkenes and alkynes with thiols.

Nat Commun 2019 Apr 15;10(1):1752. Epub 2019 Apr 15.

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, 210093, Nanjing, China.

Direct (utilize easily available and abundant precursors) and selective (both chemo- and regio-) aliphatic C-H functionalization is an attractive mean with which to streamline chemical synthesis. With many possible sites of reaction, traditional methods often need an adjacent polar directing group nearby to achieve high regio- and chemoselectivity and are often restricted to a single site of functionalization. Here we report a remote aliphatic C-H thiolation process with predictable and switchable regioselectivity through NiH-catalysed migratory hydrothiolation of two feedstock chemicals (alkenes/alkynes and thiols). Read More

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http://dx.doi.org/10.1038/s41467-019-09783-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465347PMC

Microwave-assisted synthesis and in vitro stability of N-benzylamide non-steroidal anti-inflammatory drug conjugates for CNS delivery.

Bioorg Med Chem Lett 2019 Apr 8. Epub 2019 Apr 8.

Department of Chemistry, Muhlenberg College, 2400 Chew Street, Allentown, PA 18104, United States. Electronic address:

More effective delivery of non-steroidal anti-inflammatory drugs (NSAIDs) to the brain could treat the underlying inflammatory pathology of a range of CNS diseases and conditions. Use of a blood-brain barrier shuttle such as the N-benzylamide moiety, which has been largely unexplored for this purpose, could improve the brain bioavailabilities of NSAIDs. A series of novel N-benzylamide NSAID conjugates was synthesized via a three-step process with a microwave-assisted bimolecular nucleophilic substitution as the final step. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.04.016DOI Listing

Marine Bacterium V sp. CB1-14 Produces Guanidine Alkaloid 6--Monanchorin, Previously Isolated from Marine Polychaete and Sponges.

Mar Drugs 2019 Apr 4;17(4). Epub 2019 Apr 4.

G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences,Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia.

Twenty-three bacterial strains were isolated from the secreted mucus trapping net of themarine polychaete Chaetopterus variopedatus (phylum Annelida) and twenty strains were identifiedusing 16S rRNA gene analysis. Strain CB1-14 was recognized as a new species of the genus Vibriousing the eight-gene multilocus sequence analysis (MLSA) and genome sequences of nineteen typeVibrio strains. This Vibrio sp. Read More

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http://dx.doi.org/10.3390/md17040213DOI Listing

Serial Femtosecond X-Ray Diffraction of HIV-1 Gag MA-IP6 Microcrystals at Ambient Temperature.

Int J Mol Sci 2019 Apr 3;20(7). Epub 2019 Apr 3.

Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.

The Human immunodeficiency virus-1 (HIV-1) matrix (MA) domain is involved in the highly regulated assembly process of the virus particles that occur at the host cell's plasma membrane. High-resolution structures of the MA domain determined using cryo X-ray crystallography have provided initial insights into the possible steps in the viral assembly process. However, these structural studies have relied on large and frozen crystals in order to reduce radiation damage caused by the intense X-rays. Read More

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https://www.mdpi.com/1422-0067/20/7/1675
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http://dx.doi.org/10.3390/ijms20071675DOI Listing
April 2019
2 Reads

Derivatives of the β-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer's Disease.

Molecules 2019 Apr 3;24(7). Epub 2019 Apr 3.

ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.

Twelve derivatives - of the β-crinane-type alkaloid haemanthamine were developed. All the semisynthetic derivatives were studied for their inhibitory potential against both acetylcholinesterase and butyrylcholinesterase. In addition, glycogen synthase kinase 3β (GSK-3β) inhibition potency was evaluated in the active derivatives. Read More

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http://dx.doi.org/10.3390/molecules24071307DOI Listing
April 2019
1 Read

Anti-trypanosomal activity of doubly modified salinomycin derivatives.

Eur J Med Chem 2019 Apr 3;173:90-98. Epub 2019 Apr 3.

Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61‒614, Poznań, Poland.

As a group of biologically active compounds, polyether antibiotics (ionophores) show a broad spectrum of interesting pharmacological properties, ranging from anti-bacterial to anti-cancer activities. There is increasing evidence that ionophores, including salinomycin (SAL), and their semi-synthetic analogues are promising candidates for the development of drugs against parasitic diseases. Our previous studies have shown that esterification and amidation of the C1 carboxylate moiety of SAL provides compounds with potent activity against Trypanosoma brucei, protozoan parasites responsible for African trypanosomiasis. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.061DOI Listing
April 2019
2 Reads

Preclinical Study of Biofunctional Polymer-Coated Upconversion Nanoparticles.

Toxicol Sci 2019 Apr 15. Epub 2019 Apr 15.

Nizhny Novgorod State University, Nizhny Novgorod, Russia.

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. UCNP applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. Read More

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https://academic.oup.com/toxsci/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/toxsci/kfz086DOI Listing
April 2019
5 Reads

Organocatalytic enantioselective direct alkylation of phloroglucinol derivatives: asymmetric total synthesis of (+)-aflatoxin B.

Chem Commun (Camb) 2019 Apr 15. Epub 2019 Apr 15.

School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus, Chemistry & Chemical Biology (Ministry of Education), Beijing Frontier Research, Center for biological Structure, Tsinghua University, Beijing 100084, China.

The organocatalytic enantioselective Friedel-Crafts alkylation of phloroglucinol derivatives with enals is reported, providing general access to the benzylic chiral centers shown in a variety of phloroglucinol natural products. The synthetic utility is demonstrated by the very concise asymmetric total synthesis of aflatoxins B2. Read More

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http://dx.doi.org/10.1039/c9cc01833fDOI Listing

Properties of a cryptic lysyl oxidase from haloarchaeon .

PeerJ 2019 5;7:e6691. Epub 2019 Apr 5.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.

Background: Lysyl oxidases (LOX) have been extensively studied in mammals, whereas properties and functions of recently found homologues in prokaryotic genomes remain enigmatic.

Methods: LOX open reading frame was cloned from in an expression vector. Recombinant lysyl oxidase (HTU-LOX) proteins were purified using metal affinity chromatography under denaturing conditions followed by refolding. Read More

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https://peerj.com/articles/6691
Publisher Site
http://dx.doi.org/10.7717/peerj.6691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452851PMC
April 2019
2 Reads

Production of Marker-Free Apple Plants Expressing the Supersweet Protein Gene Driven by Plant Promoter.

Front Plant Sci 2019 29;10:388. Epub 2019 Mar 29.

Laboratory of Expression Systems and Modification of the Plant Genome "Biotron", Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia.

The presence of antibiotic resistance and other marker genes in genetically modified plants causes concern in society because of perceived risks for the environment and human health. The creation of transgenic plants that do not contain foreign genetic material, especially that of bacterial and viral origin, largely alleviates the tension and makes the plants potentially more attractive for consumers. To produce marker-free transgenic apple plants, we used the pMF1 vector, which combines recombinaseR and a bifunctional selectable gene. Read More

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https://www.frontiersin.org/article/10.3389/fpls.2019.00388/
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http://dx.doi.org/10.3389/fpls.2019.00388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449483PMC
March 2019
2 Reads

Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development.

Front Cell Neurosci 2019 28;13:124. Epub 2019 Mar 28.

Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.

Adenosine receptors (ARs) function in the body's response to conditions of pathology and stress associated with a functional imbalance, such as in the supply and demand of energy/oxygen/nutrients. Extracellular adenosine concentrations vary widely to raise or lower the basal activation of four subtypes of ARs. Endogenous adenosine can correct an energy imbalance during hypoxia and other stress, for example, by slowing the heart rate by AAR activation or increasing the blood supply to heart muscle by the AAR. Read More

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http://dx.doi.org/10.3389/fncel.2019.00124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447611PMC
March 2019
2 Reads

Growth inhibition of human breast and prostate cancer cells by cinnamic acid derivatives and their mechanism of action.

Biol Pharm Bull 2019 Apr 12. Epub 2019 Apr 12.

Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University.

Cancer is the leading cause of death and there is a particularly pressing need to develop effective treatments for breast and prostate cancer. In the current study, we show the inhibitory effects of cinnamic acid derivatives, including caffeic acid phenethyl ester (CAPE, 1), on the growth of breast and prostate cancer cells. Among the compounds examined, 3,4,5-trihydroxycinnamic acid decyl ester (6) showed the most potent inhibition of cancer cell growth by the induction of apoptosis. Read More

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http://dx.doi.org/10.1248/bpb.b18-01002DOI Listing

Seed germination, respiratory processes and phosphatidic acid accumulation in Arabidopsis diacylglycerol kinase knockouts - The effect of brassinosteroid, brassinazole and salinity.

Steroids 2019 Apr 11. Epub 2019 Apr 11.

Department of the Molecular Mechanisms of Cell Metabolism Regulation, Kukhar Institute of Bioorganic Chemistry and Petrochemistry, The National Academy of Sciences of Ukraine, 02660, Murmanska str., 1, Kyiv, Ukraine. Electronic address:

Using Arabidopsis thaliana wild type (WT) plants and diacylglycerol kinase knockouts (single mutants - dgk3, dgk1, dgk6; double mutants - dgk3dgk7, dgk5dgk6, dgk1dgk2) we observed that the inhibitor of brassinosteroid (BR) biosynthesis, brassinazole (BRZ), drastically decreased germination of dgk mutants under salt stress, while BRZ co-administration with 24-epibrassinolide (EBL) partially improved germination rates. We also observed a statistically significant decrease in alternative and cytochrome respiratory pathways in response to BRZ treatment under salinity conditions. We showed that production of the lipid second messenger phosphatidic acid (PA) is impaired in dgk mutants in response to EBL treatment and inhibitor of diacylglycerol kinase (DGK) - R59022. Read More

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http://dx.doi.org/10.1016/j.steroids.2019.04.002DOI Listing

Synthesis of diphenoxyadamantane alkylamines with pharmacological interest.

Bioorg Med Chem Lett 2019 Apr 6. Epub 2019 Apr 6.

Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1 E7HT, UK.

In this work, the synthesis and the pharmacological evaluation of diphenoxyadamantane alkylamines Ia-f and IIa-f is described. The new diphenoxy-substituted adamantanes share structural features present in trypanocidal and antitubercular agents. 1-Methylpiperazine derivative Ia is the most potent against T. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.04.010DOI Listing
April 2019
2.420 Impact Factor

Massive Cryptosporidium infections and chronic diarrhea in HIV-negative patients.

Parasitol Res 2019 Apr 12. Epub 2019 Apr 12.

Department and Clinic of Tropical and Parasitic Diseases, Poznań University of Medical Sciences, Przybyszewskiego Street, 60-355, Poznań, Poland.

Protozoa of the genus Cryptosporidium are common parasites of domestic and wild animals-mammals, birds, reptiles, and fishes. The invasive forms are thick-walled oocysts, which can be present in water supplies, on fruits, vegetables, or in the soil contaminated with feces. In this work, we describe three cases of middle-aged persons with massive Cryptosporidium hominis infection and chronic diarrhea with no immunological abnormalities and no history of previous travels to tropical countries. Read More

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http://dx.doi.org/10.1007/s00436-019-06302-0DOI Listing
April 2019
3 Reads

Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells.

Cell Death Differ 2019 Apr 11. Epub 2019 Apr 11.

NCI Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.

Most caspases can be positioned unambiguously within the regulated cell death networks of apoptosis and pyroptosis, but the role of caspase-2, a highly conserved protease within the family, remains enigmatic. This is mainly due to lack of selective chemical and biochemical tools for the investigation of this protease. In this study, we used our hybrid combinatorial substrate library (HyCoSuL) approach to broadly profile caspase-2 substrate specificity using peptide scanning libraries. Read More

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http://dx.doi.org/10.1038/s41418-019-0329-2DOI Listing

Four N-(E)-cinnamoyl (cinnamamide) derivatives of aminoalkanols with promising anticonvulsant and analgesic activity.

Bioorg Med Chem Lett 2019 Apr 4. Epub 2019 Apr 4.

Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.

Epilepsy and neuropathic pain are frequent neurological disorders with pathomechanism based on abnormal neuronal discharges. Secondary tissue impairment observed after traumatic brain injury is also connected with neuronal dysfunction. Those three neurological disorders are ineffectively treated with currently available pharmacotherapy options so great effort is made in searching for new effective drugs. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.04.006DOI Listing

Immunoreactivity changes of human serum albumin and alpha-1-microglobulin induced by their interaction with dendrimers.

Colloids Surf B Biointerfaces 2019 Apr 4;179:226-232. Epub 2019 Apr 4.

Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. Electronic address:

Dendrimers are hyperbranched polymers for delivery of therapeutic genetic material to cancer cells. The fine tuning chemical modifications of dendrimers allow for the modification of the composition. The architecture and the properties of dendrimers are key factors to improve their in vitro and in vivo properties such as biocompatibility with cells and tissues and their pharmacokinetic/pharmacodynamic behavior. Read More

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http://dx.doi.org/10.1016/j.colsurfb.2019.03.065DOI Listing
April 2019
1 Read

Hybrid design of isonicotinic acid hydrazide derivatives: machine learning studies, synthesis and biological evaluation of their anti-tuberculosis activity.

Curr Drug Discov Technol 2019 Apr 11. Epub 2019 Apr 11.

V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, 1 Murmanska Street, 02660, Kyiv. Ukraine.

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs.

Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Read More

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http://dx.doi.org/10.2174/1570163816666190411110331DOI Listing
April 2019
4 Reads