491 results match your criteria site 3-position


Unexpected Substituent Effects in Spiro-Compound Formation: Steering -Aryl Propynamides and DMSO toward Site-Specific Sulfination in Quinolin-2-ones or Spiro[4,5]trienones.

J Org Chem 2021 Jul 29;86(14):9490-9502. Epub 2021 Jun 29.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.

A highly substituent-dependent rearrangement allows for the novel and SOCl-induced divergent synthesis of 3-methylthioquinolin-2-ones and 3-methylthiospiro[4.5]trienones through intramolecular electrophilic cyclization of -aryl propyamides. DMSO acts as both solvent and sulfur source, and use of DMSO-/ enables the incorporation of SCH or SCD moieties to the 3-position of the heterocyclic framework. Read More

View Article and Full-Text PDF

Mechanism of Inhibition of the Reproduction of SARS-CoV-2 and Viruses by Remdesivir.

Biochemistry 2021 06 10;60(24):1869-1875. Epub 2021 Jun 10.

Department of Chemistry, Yale University, New Haven, Connecticut 06511-8499, United States.

Remdesivir is an antiviral drug initially designed against the virus. The results obtained with it both in biochemical studies and in cell line assays were very promising, but it proved to be ineffective in clinical trials. Remdesivir exhibited far better efficacy when repurposed against SARS-CoV-2. Read More

View Article and Full-Text PDF

Selective Bacterial Targeting and Infection-Triggered Release of Antibiotic Colistin Conjugates.

Angew Chem Int Ed Engl 2021 Jun 7. Epub 2021 Jun 7.

Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany.

In order to render potent, but toxic antibiotics more selective, we have explored a novel conjugation strategy that includes drug accumulation followed by infection-triggered release of the drug. Bacterial targeting was achieved using a modified fragment of the human antimicrobial peptide ubiquicidin, as demonstrated by fluorophore-tagged variants. To limit the release of the effector colistin only to infection-related situations, we introduced a linker that was cleaved by neutrophil elastase (NE), an enzyme secreted by neutrophil granulocytes at infection sites. Read More

View Article and Full-Text PDF

[Interaction of IL-6 gene with tumor necrosis factor-α and white blood cell in metabolic syndrome].

Wei Sheng Yan Jiu 2021 Mar;50(2):261-273

School of Public Health, Ningxia Medical University, Yinchuan 750004, China.

Objective: To investigate the associations between the polymorphisms and interaction of the interleukin 6(IL-6) genes at-634 C/G, -174 G/C, -1363 G/T loci, as well as the interactions between the three loci and tumor necrosis factor(TNF-α), and peripheral blood leukocytes(white blood cell, WBC) with metabolic syndrome(MS).

Methods: Using the case-control research method, according to the inclusion and exclusion criteria, from March 2015 to March 2016 from the General Hospital of Ningxia Medical University and Wuzhong City People's Hospital, 376 unrelated cases and 408 control groups were selected. We conducted questionnaire surveys(including general conditions, disease and medication history, family history, etc. Read More

View Article and Full-Text PDF

The Photosystem II Assembly Factor Ycf48 from the Cyanobacterium sp. PCC 6803 Is Lipidated Using an Atypical Lipobox Sequence.

Int J Mol Sci 2021 Apr 2;22(7). Epub 2021 Apr 2.

Centre Algatech, Laboratory of Photosynthesis, Institute of Microbiology of the Czech Academy of Sciences, Opatovický mlýn, 37981 Třeboň, Czech Republic.

Photochemical energy conversion during oxygenic photosynthesis is performed by membrane-embedded chlorophyll-binding protein complexes. The biogenesis and maintenance of these complexes requires auxiliary protein factors that optimize the assembly process and protect nascent complexes from photodamage. In cyanobacteria, several lipoproteins contribute to the biogenesis and function of the photosystem II (PSII) complex. Read More

View Article and Full-Text PDF

Homology Model of a Catalytically Competent Bifunctional Rel Protein.

Front Mol Biosci 2021 3;8:628596. Epub 2021 Feb 3.

Department of Chemistry, Università Degli Studi di Milano, Milan, Italy.

Bacteria have developed different bet hedging strategies to survive hostile environments and stressful conditions with persistency being maybe the most elegant yet still poorly understood one. Persisters' temporary tolerance to antibiotic treatment hints at their role not only in chronic and recurrent infections but also in the insurgence of resistant strains. Therefore, hampering persisters formation might represent an innovative strategy in the quest for new effective antimicrobial compounds. Read More

View Article and Full-Text PDF
February 2021

Rh(III)-Catalyzed Redox-Neutral C-H Activation/[3 + 2] Annulation of -Phenoxy Amides with Propargylic Monofluoroalkynes.

Org Lett 2021 03 3;23(6):2285-2291. Epub 2021 Mar 3.

Key Laboratory of Molecular Target & Clinical Pharmacology and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.

An efficient and redox-neutral Rh(III)-catalyzed C-H activation/[3 + 2] annulation of -phenoxy amides with propargylic monofluoroalkynes has been realized to afford 3-alkylidene dihydrobenzofurans with an interesting α-quaternary carbon center. Combined experimental and computational mechanistic studies revealed that a Rh(III)-Rh(V)-Rh(III) catalytic pathway/uncatalyzed intramolecular [H···F] bonding-assisted S2'-type substitution cascade might be involved in the catalytic cycle, thereby enabling an excellent site-/regioselectivity with broad substrate/functional group compatibility, including the complete retention of the highly strained cyclobutyl structure in the 3-position. Read More

View Article and Full-Text PDF

How Do Electrostatic Perturbations of the Protein Affect the Bifurcation Pathways of Substrate Hydroxylation versus Desaturation in the Nonheme Iron-Dependent Viomycin Biosynthesis Enzyme?

J Phys Chem A 2021 Mar 23;125(8):1720-1737. Epub 2021 Feb 23.

Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.

The viomycin biosynthesis enzyme VioC is a nonheme iron and α-ketoglutarate-dependent dioxygenase involved in the selective hydroxylation of l-arginine at the C-position for antibiotics biosynthesis. Interestingly, experimental studies showed that using the substrate analogue, namely, l-homo-arginine, a mixture of products was obtained originating from C-hydroxylation, C-hydroxylation, and C-C-desaturation. To understand how the addition of one CH group to a substrate can lead to such a dramatic change in selectivity and activity, we decided to perform a computational study using quantum mechanical (QM) cluster models. Read More

View Article and Full-Text PDF

Impact of Glycan Linkage to Wall Teichoic Acid on Langerin Recognition and Langerhans Cell Activation.

ACS Infect Dis 2021 03 16;7(3):624-635. Epub 2021 Feb 16.

Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.

is the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond to invading and contribute to an effective immune response. Langerhans cells (LCs), the only professional antigen-presenting cell type in the epidermis, sense through their pattern-recognition receptor langerin, triggering a proinflammatory response. Read More

View Article and Full-Text PDF

Probing the Binding Requirements of Modified Nucleosides with the DNA Nuclease SNM1A.

Molecules 2021 Jan 9;26(2). Epub 2021 Jan 9.

School of Chemistry and Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St., D02 R590 Dublin, Ireland.

SNM1A is a nuclease that is implicated in DNA interstrand crosslink repair and, as such, its inhibition is of interest for overcoming resistance to chemotherapeutic crosslinking agents. However, the number and identity of the metal ion(s) in the active site of SNM1A are still unconfirmed, and only a limited number of inhibitors have been reported to date. Herein, we report the synthesis and evaluation of a family of malonate-based modified nucleosides to investigate the optimal positioning of metal-binding groups in nucleoside-derived inhibitors for SNM1A. Read More

View Article and Full-Text PDF
January 2021

'Proximity frequencies' a new parameter to evaluate the profile of GABAR modulators.

Bioorg Med Chem Lett 2021 02 4;34:127755. Epub 2021 Jan 4.

Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section, University of Florence, Sesto Fiorentino, Italy. Electronic address:

We reported the synthesis of new 8-methoxypyrazolo[1,5-a]quinazolines bearing an amide fragment at the 3-position. The final compounds, as aromatic (2a-i) and 4,5-dihydro derivatives (3a-i), have been evaluated in vitrofor their ability to modulate the chlorine current on recombinant GABA receptors of the α1β2γ2L type (expressed in frog oocytes of the Xenopus laevis species). From electrophysiological test two groups of compounds emerged: positive modulators agonist (2e, h, i and 3e, h) and null modulators antagonist (2a, b, d, f, g and 3a-d, f, g) of GABA subtype receptor. Read More

View Article and Full-Text PDF
February 2021

SAR Investigation and Discovery of Water-Soluble 1-Methyl-1,4-dihydroindeno[1,2-]pyrazoles as Potent Tubulin Polymerization Inhibitors.

J Med Chem 2020 12 17;63(23):14840-14866. Epub 2020 Nov 17.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, P. R. China.

Taking the previously discovered 1-methyl-1,4-dihydroindeno[1,2]pyrazol derivative LL01 as a lead, systematic structural modifications were made at the phenolic 6- and 7-positions and the aniline at the 3-position of the indenopyrazole core to investigate the SARs and to improve water solubility. Among the designed indenopyrazoles -, a series of potent MTAs were identified. As the hydrochloride salt(s), and showed excellent aqueous solubility and favorable Log  value and displayed noteworthily low nanomolar potency against a variety of tumor cells, including those taxol-resistant ones. Read More

View Article and Full-Text PDF
December 2020

Enhanced Production of Active Ecumicin Component with Higher Antituberculosis Activity by the Rare Actinomycete sp. MJM5123 Using a Novel Promoter-Engineering Strategy.

ACS Synth Biol 2020 11 25;9(11):3019-3029. Epub 2020 Sep 25.

Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 17058, Republic of Korea.

Ecumicins are potent antituberculosis natural compounds produced by the rare actinomycete sp. MJM5123. Here, we report an efficient genetic manipulation platform of this rare actinomycete. Read More

View Article and Full-Text PDF
November 2020

Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation.

Int J Biol Macromol 2020 Dec 11;164:1927-1938. Epub 2020 Aug 11.

School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, People's Republic of China; State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, People's Republic of China. Electronic address:

This study aimed to reveal the interaction and inhibitory mechanisms of tangeretin (TAN), nobiletin (NBT), and their acidic hydroxylated forms, 5-demethyltangeretin (5-DT) and 5-demethylnobiletin (5-DN) on porcine pancreatic lipase (PPL) using spectroscopic techniques and molecular dynamics (MD) simulation. PPL inhibition assay showed that the inhibitory activity of NBT (IC value of 3.60 ± 0. Read More

View Article and Full-Text PDF
December 2020

Structural basis for the stabilization of amyloidogenic immunoglobulin light chains by hydantoins.

Bioorg Med Chem Lett 2020 08 16;30(16):127356. Epub 2020 Jun 16.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:

Misfolding and aggregation of immunoglobulin light chains (LCs) leads to the degeneration of post-mitotic tissue in the disease immunoglobulin LC amyloidosis (AL). We previously reported the discovery of small molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which slow or stop the LC aggregation cascade at the outset. A predominant structural category of kinetic stabilizers emerging from the high-throughput screen are coumarins substituted at the 7-position, which bind at the interface between the two variable domains of the light chain dimer. Read More

View Article and Full-Text PDF

Effect of changes at the conserved + 3 position of mature archaellins on in vitro cleavage by the pre-archaellin peptidase FlaK of Methanococcus maripaludis.

Authors:
Ken F Jarrell

Arch Microbiol 2020 Sep 13;202(7):1669-1675. Epub 2020 Apr 13.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, K7L 3N6, Canada.

Archaea swim using archaella that are domain-specific rotary type IV pilus-like appendages. The structural components of the archaellum filament are archaellins, initially made as preproteins with type IV pilin-like signal peptides which are removed by signal peptidases that are homologues of prepilin peptidases that remove signal peptides from type IV pilins. N-terminal sequences of archaellins, including the signal peptide cleavage site, are conserved and various positions have been previously shown to be critical for signal peptide removal. Read More

View Article and Full-Text PDF
September 2020

Synthesis and Biological Evaluation of New Antitubulin Agents Containing 2-(3',4',5'-trimethoxyanilino)-3,6-disubstituted-4,5,6,7-tetrahydrothieno[2,3-]pyridine Scaffold.

Molecules 2020 Apr 7;25(7). Epub 2020 Apr 7.

Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, 44121 Ferrara, Italy.

Two novel series of compounds based on the 4,5,6,7-tetrahydrothieno[2,3-]pyridine and 4,5,6,7-tetrahydrobenzo[]thiophene molecular skeleton, characterized by the presence of a 3',4',5'-trimethoxyanilino moiety and a cyano or an alkoxycarbonyl group at its 2- or 3-position, respectively, were designed, synthesized, and evaluated for antiproliferative activity on a panel of cancer cell lines and for selected highly active compounds, inhibition of tubulin polymerization, and cell cycle effects. We have identified the 2-(3',4',5'-trimethoxyanilino)-3-cyano-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-]pyridine derivative and its 6-ethoxycarbonyl homologue as new antiproliferative agents that inhibit cancer cell growth with IC values ranging from 1.1 to 4. Read More

View Article and Full-Text PDF

Combining mutagenesis on Glu281 of prenyltransferase NovQ and metabolic engineering strategies for the increased prenylated activity towards menadione.

Appl Microbiol Biotechnol 2020 May 3;104(10):4371-4382. Epub 2020 Mar 3.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei, 230031, Anhui, People's Republic of China.

Prenyltransferase NovQ is a vital class involved in the biosynthesis of secondary metabolites such as clorobiocin and novobiocin. To investigate the relationship between structure and catalytic properties of NovQ, here, we have analyzed the substrate-binding site, namely PT barrel, and revealed that menadione hydroquinol formed intermolecular interactions with the residue Glu281 near the center of the active pocket. In this study, Glu281 was substituted with 9 diverse amino acids and catalytic properties of mutants were observed in vitro. Read More

View Article and Full-Text PDF

A Thioxanthone Sensitizer with a Chiral Phosphoric Acid Binding Site: Properties and Applications in Visible Light-Mediated Cycloadditions.

Chemistry 2020 Apr 15;26(23):5190-5194. Epub 2020 Apr 15.

Department of Chemistry and Catalysis Research Center (CRC), Technical University Munich, Lichtenbergstr. 4, 85747, Garching, Germany.

A chiral phosphoric acid with a 2,2'-binaphthol core was prepared that displays two thioxanthone moieties at the 3,3'-position as light-harvesting antennas. Despite its relatively low triplet energy, the phosphoric acid was found to be an efficient catalyst for the enantioselective intermolecular [2+2] photocycloaddition of β-carboxyl-substituted cyclic enones (e.r. Read More

View Article and Full-Text PDF

A childhood-onset nemaline myopathy caused by novel heterozygote variants in the nebulin gene with literature review.

Acta Neurol Belg 2020 Dec 6;120(6):1351-1360. Epub 2019 Nov 6.

Department of Neurology, First Hospital, Shanxi Medical University, Taiyuan, 030000, People's Republic of China.

Nemaline myopathy, a rare congenital myopathy, is characterized by generalized muscle weakness, hypotonia, respiratory insufficiency, and the presence of rod structures on muscle biopsy, which is caused by mutations in at least 13 known genes. A patient showing gradually deteriorated proximal muscle weakness and rod-shaped structures found in muscle fibers was suspected of having nemaline myopathy, following by the next-generation sequencing. We report two novel compound heterozygous variants in nebulin gene in a family residing in China. Read More

View Article and Full-Text PDF
December 2020

Influence of age, laterality, patient position, and spinal level on the interlamina space for spinal puncture.

Reg Anesth Pain Med 2019 Nov 4. Epub 2019 Nov 4.

Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, South Korea

Background And Objectives: The lumbar interlamina space height is an important determinant of successful spinal puncture. We aimed to evaluate the influence of age, laterality, patient position, and spinal level on the height of the interlamina window using ultrasonography.

Methods: Ultrasonographic examination was performed in 20 adult patients aged under 40 years (group Y) and 20 patients aged over 60 years (group O). Read More

View Article and Full-Text PDF
November 2019

UV Resonance Raman Characterization of a Substrate Bound to Human Indoleamine 2,3-Dioxygenase 1.

Biophys J 2019 08 19;117(4):706-716. Epub 2019 Jul 19.

Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo, Japan.

Human indoleamine 2,3-dioxygenase 1 (IDO) is a heme enzyme that catalyzes the first reaction of the main metabolic pathway of L-tryptophan (Trp) to produce N-formylkynurenin. The reaction involves cleavage of the C=C bond in the Trp indole ring and insertion of two atomic oxygens from the iron-bound O into the indole 2 and 3 position. For establishment of the chemical mechanism of this unique enzymatic reaction, it is necessary to determine the conformation and electronic state of the substrate Trp bound to IDO. Read More

View Article and Full-Text PDF

Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs.

Elife 2019 05 24;8. Epub 2019 May 24.

Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.

Human NimA-related kinases (Neks) have multiple mitotic and non-mitotic functions, but few substrates are known. We systematically determined the phosphorylation-site motifs for the entire Nek kinase family, except for Nek11. While all Nek kinases strongly select for hydrophobic residues in the -3 position, the family separates into four distinct groups based on specificity for a serine versus threonine phospho-acceptor, and preference for basic or acidic residues in other positions. Read More

View Article and Full-Text PDF

Impact of Benzannulation Site at the Diimine (N^N) Ligand on the Excited-State Properties and Reverse Saturable Absorption of Biscyclometalated Iridium(III) Complexes.

Inorg Chem 2019 May 23;58(9):5483-5493. Epub 2019 Apr 23.

Department of Chemistry and Biochemistry , North Dakota State University , Fargo , North Dakota 58108-6050 , United States.

Ten biscyclometalated monocationic Ir(III) complexes were synthesized and studied to elucidate the effects of extending π-conjugation of the diimine ligand (N^N = 2,2'-bipyridine in Ir1, 2-(pyridin-2-yl)quinoline in Ir2, 2-(pyridin-2-yl)[6,7]benzoquinoline in Ir3, 2-(pyridin-2-yl)-[7,8]benzoquinoline in Ir4, phenanthroline in Ir5, benzo[ f][1,10]phenanthroline in Ir6, naphtho[2,3- f][1,10]phenanthroline in Ir7, 2,2'-bisquinoline in Ir8, 3,3'-biisoquinoline in Ir9, and 1,1'-biisoquinoline in Ir10) via benzannulation at 2,2'-bipyridine on the excited-state properties and reverse saturable absorption (RSA) of these complexes. Either a bathochromic or a hypsochromic shift of the charge-transfer absorption band and emission spectrum was observed depending on the benzannulation site at the 2,2'-bipyridine ligand. Benzannulation at the 3,4-/3',4'-position or 5,6-/5',6'-position of 2,2'-bipyridine ligand or at the 6,7-position of the quinoline ring on the N^N ligand caused red-shifted charge-transfer absorption band and emission band for complexes Ir2, Ir8, Ir10 vs Ir1 and Ir3 vs Ir2, while benzannulation at the 4,5-/4',5'-position of 2,2'-bipyridine ligand or at the 7,8-position of the quinoline ring on the N^N ligand induced a blue shift of the charge-transfer absorption and emission bands for complex Ir9 vs Ir1 and Ir4 vs Ir2. Read More

View Article and Full-Text PDF

A Bis-Zn -Pyridyl-Salen-Type Complex Conjugated to the ATP Aptamer: An ATPase-Mimicking Nucleoapzyme.

Chembiochem 2020 01 24;21(1-2):53-58. Epub 2019 Jun 24.

Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.

Catalytic nucleic acids consisting of a bis-Zn -pyridyl-salen-type ([di-Zn 3,5 bis(pyridinylimino) benzoic acid]) complex conjugated to the ATP aptamer act as ATPase-mimicking catalysts (nucleoapzymes). Direct linking of the Zn complex to the 3'- or 5'-end of the aptamer (nucleoapzymes I and II) or its conjugation to the 3'- or 5'-end of the aptamer through bis-thymidine spacers (nucleoapzymes III and IV) provided a set of nucleoapzymes exhibiting variable catalytic activities. Whereas the separated bis-Zn -pyridyl-salen-type catalyst and the ATP aptamer do not show any noticeable catalytic activity, the 3'-catalyst-modified nucleoapzyme (nucleoapzyme IV) and, specifically, the nucleoapzyme consisting of the catalyst linked to the 3'-position through the spacer (nucleoapzyme III) reveal enhanced catalytic features in relation to the analogous nucleoapzyme substituted at the 5'-position (k =4. Read More

View Article and Full-Text PDF
January 2020

Synthesis and antibacterial activity of novel icariin derivatives.

Authors:
A Wang Y Xu

Pharmazie 2019 02;74(2):73-78

A series of aromatic sulfonyls substituted icariin derivatives was synthesized and their antibacterial activities against (including drug-sensitive bacteria and drug-resistant bacteria) were evaluated. Among them, compound exhibited high potency against methicillin-sensitive (MSSA) and resistant strains of (MRSA) with MIC values of 1-2 mmol/L. Reverse virtual screening and molecule docking analysis indicated that compound might bind the allosteric site of PBP2a that may inhibit cell wall synthesis, with the advantage of activity against multidrug resistant SPR experiment further confirmed the binding affinity. Read More

View Article and Full-Text PDF
February 2019

Diarylborinic Acid-Catalyzed, Site-Selective Sulfation of Carbohydrate Derivatives.

J Org Chem 2019 01 8;84(2):900-908. Epub 2019 Jan 8.

Department of Chemistry , University of Toronto , 80 St. George St. , Toronto , ON M5S 3H6 , Canada.

Sulfated carbohydrates have been implicated in diverse biological processes, with the position and extent of sulfation of a glycoside often playing important roles in determining the affinity and specificity of its binding to a biomolecular partner. Methods for the site-selective introduction of sulfate groups to carbohydrates are thus of interest. Here, we describe the development of a diarylborinic acid-catalyzed protocol for selective sulfation of pyranoside derivatives at the equatorial position of a cis-1,2-diol group. Read More

View Article and Full-Text PDF
January 2019

C-3- and C-4-Substituted Bicyclic Coumarin Sulfamates as Potent Steroid Sulfatase Inhibitors.

ACS Omega 2018 Sep 6;3(9):10748-10772. Epub 2018 Sep 6.

Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.

Synthetic routes to potent bicyclic nonsteroidal sulfamate-based active-site-directed inhibitors of the enzyme steroid sulfatase (STS), an emerging target in the treatment of postmenopausal hormone-dependent diseases, including breast cancer, are described. Sulfamate analogs - and - of the core in vivo active two-ring coumarin template, modified at the 4- and 3-positions, respectively, were synthesized to expand structure-activity relationships. α-Alkylacetoacetates were used to synthesize coumarin sulfamate derivatives with 3-position modifications, and the bicyclic ring of other parent coumarins was primarily constructed via the Pechmann synthesis of hydroxyl coumarins. Read More

View Article and Full-Text PDF
September 2018

Scaffold hopping-guided design of some isatin based rigid analogs as fatty acid amide hydrolase inhibitors: Synthesis and evaluation.

Biomed Pharmacother 2018 Nov 7;107:1611-1623. Epub 2018 Sep 7.

Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, Uttar Pradesh, India. Electronic address:

Fatty acid amide hydrolase (FAAH) represents a potential therapeutic target for number of peripheral and nervous system related disorders including neuropathic pain and neuroinflammation. A library of N-(2,4-dichlorobenzoyl) isatin Schiff bases 7a-7l and 8a-8c were designed using the contemporary scaffold-hopping approach, synthesized and investigated for their ability to inhibit human FAAH enzyme using fluorescence based Cayman assay kit. The synthesized compounds inhibited FAAH with IC values in the range from 1. Read More

View Article and Full-Text PDF
November 2018

Data on the UV filtering and radical scavenging capacity of the bitter masking flavanone Eriodictyol.

Data Brief 2018 Oct 31;20:981-985. Epub 2018 Aug 31.

Department of Chemistry, University of Calicut, Malappuram 673635, India.

A computational analysis of UV filtering and radical scavenging capacity of a flavanone, Eriodictyol has been performed under DFT-B3LYP/6-31+ G (d, p). Eriodictyol is nontoxic and nonirritant bitter masker used in wine and can be used for photo protection due to its potential UV filtering and radical scavenging capacity. The compound has an absorbance in the UV-A and UV-B region of electromagnetic spectrum, it can be used as a potential UV filter in sunscreen lotions and other cosmetic products. Read More

View Article and Full-Text PDF
October 2018