Use of a deoxynojirimycin-fluorophore conjugate as a cell-specific imaging probe targeting α-glucosidase on cell membranes.

Abstract:

:Molecules designed for cell-specific imaging were studied, taking advantage of an enzyme-inhibitor interaction. 1-Deoxynojirimycin (DNJ) can be actively captured by cells which express the surface membrane protein α-glucosidase. New probes composed of DNJ for recognition linked to a fluorophore signal portion were prepared (DNJ-CF31, DNJ-Dans 2 and DNJ-DEAC 3). Docking simulations revealed that the inhibitors acarbose and miglitol and the inhibitor portion of the probes bind at the same position in the pocket of α-glucosidase (human-derived PDB: 3TON). The ability of probes 1-3 to detect the difference between HeLa cells (from human cervical cancer tissue), Neuro-2a cells (from a mouse neuroblastoma C1300 tumor), N1E-115 cells (from a mouse brain neuroblastoma C1300 tumor), A1 cells (from the astrocyte of a newborn mouse brain), and Caco-2 cells (from a human colon carcinoma) was evaluated, and cell-specific fluorescence imaging was possible for conjugate probes 1 and 2. Caco-2 cells treated with probes 1 and 2 showed blue and green fluorescence, respectively, from the cell membrane, and did not stain the Caco-2 cells inside. These results show that DNJ-CF31 and DNJ-Dans 2 recognize an α-glucosidase protein on the surface of Caco-2 cells. Probes 1 and 2 did not stain any part of the other cells. This cell-specific imaging strategy is applicable for a variety of therapeutic agents for many diseases.

journal_name

Bioorg Med Chem

authors

Hatano A,Kanno Y,Kondo Y,Sunaga Y,Umezawa H,Fukui K

doi

10.1016/j.bmc.2019.01.032

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

859-864

issue

5

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(18)31708-5

journal_volume

27

pub_type

杂志文章
  • Synthesis of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives as inhibitors of human liver glycogen phosphorylase a.

    abstract::A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC(50) of 0.90microM. The pyridine analogue of 2f show...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.04.010

    authors: Onda K,Suzuki T,Shiraki R,Yonetoku Y,Negoro K,Momose K,Katayama N,Orita M,Yamaguchi T,Ohta M,Tsukamoto S

    更新日期:2008-05-15 00:00:00

  • Vinyldiaminotriazine-acridine conjugate as G-quadruplex alkylating agent.

    abstract::Higher-order structures of nucleic acids have become widely noted for their biological consequences and the discovery of an alkylating small molecule for these structures has been of interest due to its therapeutic potential. We previously developed the vinyldiaminotriazine (VDAT)-acridine conjugate as a T-T mismatch ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.05.030

    authors: Hazemi ME,Onizuka K,Kobayashi T,Usami A,Sato N,Nagatsugi F

    更新日期:2018-07-23 00:00:00

  • Engineered production of cancer targeting peptide (CTP)-containing C-1027 in Streptomyces globisporus and biological evaluation.

    abstract::Conjugation of cancer targeting peptides (CTPs) with small molecular therapeutics has emerged as a promising strategy to deliver potent (but typically nonspecific) cytotoxic agents selectively to cancer cells. Here we report the engineered production of a CTP (NGR)-containing C-1027 and evaluation of its activity agai...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.04.017

    authors: Li W,Li X,Huang T,Teng Q,Crnovcic I,Rader C,Shen B

    更新日期:2016-09-01 00:00:00

  • Developing new chemical tools for DNA methyltransferase 1 (DNMT 1): a small-molecule activity-based probe and novel tetrazole-containing inhibitors.

    abstract::DNA methylation is an important epigenetic modification catalyzed by DNA methyltransferases (DNMTs). Abnormal expression of endogenous DNMTs in human causes alterations in the genome methylation patterns which subsequently lead to the development of cancers. Thus detection of endogenous DNMT activities and efficient i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.03.006

    authors: Zhu B,Ge J,Yao SQ

    更新日期:2015-06-15 00:00:00

  • G-quadruplex DNA cleavage preference and identification of a perylene diimide G-quadruplex photocleavage agent using a rapid fluorescent assay.

    abstract::A rapid fluorescence assay for G-quadruplex DNA cleavage was used to investigate the preference of TMPyP4 photochemical and Mn·TMPyP4 oxidative cleavage. Both agents most efficiently cleave the c-Myc promoter G-quadruplex. Direct PAGE analysis of selected assay samples showed that for a given cleavage agent, different...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.10.017

    authors: Schoonover M,Kerwin SM

    更新日期:2012-12-15 00:00:00

  • Identification of sortase substrates by specificity profiling.

    abstract::Sortases catalyze the attachment of surface proteins to the peptidoglycan layer of gram-positive bacteria and further represent powerful tools of protein chemistry. During catalysis sortases cleave a donor substrate containing the LPxTG (x=any amino acid) sorting motif under formation of an enzyme-bound thioester and ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.06.033

    authors: Schmohl L,Bierlmeier J,von Kügelgen N,Kurz L,Reis P,Barthels F,Mach P,Schutkowski M,Freund C,Schwarzer D

    更新日期:2017-09-15 00:00:00

  • Radiofluorinated histamine H₃ receptor antagonist as a potential probe for in vivo PET imaging: radiosynthesis and pharmacological evaluation.

    abstract::The histamine H(3) receptor (H(3)R) plays a role in cognition and memory processes and is implicated in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. In vivo studies of the H(3)R occupancy using a radiolabeled PET tracer would be very useful for CNS drug discovery and ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.03.024

    authors: Selivanova SV,Honer M,Combe F,Isensee K,Stark H,Krämer SD,Schubiger PA,Ametamey SM

    更新日期:2012-05-01 00:00:00

  • Synthesis and biological activity of a fluorescent schweinfurthin analogue.

    abstract::Most of the natural schweinfurthins are potent and selective inhibitors of cell growth as measured by the National Cancer Institute's 60-cell line screen. Due to the limited supply of these natural products, we have initiated a program aimed at their synthesis. To date, this effort has led to the preparation of three ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.04.071

    authors: Kuder CH,Neighbors JD,Hohl RJ,Wiemer DF

    更新日期:2009-07-01 00:00:00

  • Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor.

    abstract::P38α/MAPK14 is intracellular signalling regulator involved in biosynthesis of inflammatory mediator cytokines (TNF-α, IL-1, IL-6, and IL-1b), which induce the production of inflammatory proteins (iNOS, NF-kB, and COX-2). In this study, drug repurposing strategies were followed to repositioning of a series of B-RAF V60...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115969

    authors: Ali EMH,Abdel-Maksoud MS,Hassan RM,Mersal KI,Ammar UM,Se-In C,He-Soo H,Kim HK,Lee A,Lee KT,Oh CH

    更新日期:2021-02-01 00:00:00

  • Design, synthesis and molecular docking of α,β-unsaturated cyclohexanone analogous of curcumin as potent EGFR inhibitors with antiproliferative activity.

    abstract::A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.11.031

    authors: Xu YY,Cao Y,Ma H,Li HQ,Ao GZ

    更新日期:2013-01-15 00:00:00

  • Synthesis and antiproliferative activity of sulfonamide-based peptidomimetic calpain inhibitors.

    abstract::The calpains are a conserved family of cysteine proteases that includes several isoforms of which µ-calpain and m-calpain are the most widely distributed in mammalian cells. Calpains have been implicated in normal physiological processes as well as cellular abnormalities such as neurodegenerative disorders, cataract, ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115433

    authors: Donkor IO,Xu J,Liu J,Cameron K

    更新日期:2020-05-01 00:00:00

  • Tetraketones: a new class of tyrosinase inhibitors.

    abstract::Twenty-eight tetraketones (1-28) with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors. Remarkably compounds 25 (IC(50)=2.06 microM), 11 (IC(50)=2.09 microM), 15 (IC(50)=2.61 microM), and 27 (IC(50)=3.19 microM) were found to be the most active compounds of the series, even better t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.08.029

    authors: Khan KM,Maharvi GM,Khan MT,Jabbar Shaikh A,Perveen S,Begum S,Choudhary MI

    更新日期:2006-01-15 00:00:00

  • Synthesis and anticonvulsant activity of new N-Mannich bases derived from 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine-2,5-diones. Part II.

    abstract::Synthesis and anticonvulsant activity of new N-Mannich bases of 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine-2,5-diones have been described. Initial anticonvulsant screening was performed in mice after intraperitoneal administration in the maximal electroshock seizure test (MES) and subcutaneous pentylenetetr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.05.032

    authors: Obniska J,Rzepka S,Kamiński K

    更新日期:2012-08-01 00:00:00

  • Synthesis and biological evaluation of 18F-labled 2-phenylindole derivatives as PET imaging probes for β-amyloid plaques.

    abstract::A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as β-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for Aβ(1-42) aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with (18)F ([(18)F]1a) for its high affinit...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.04.028

    authors: Fu H,Yu L,Cui M,Zhang J,Zhang X,Li Z,Wang X,Jia J,Yang Y,Yu P,Jia H,Liu B

    更新日期:2013-07-01 00:00:00

  • Novel 6-hydroxy-3-morpholinones as cornea permeable calpain inhibitors.

    abstract::A novel series of 6-hydroxy-3-morpholinones, in which the functional aldehyde and the hydroxy group of P(2) site form a cyclic hemiacetal, was identified as calpain inhibitors. The placement of isobutyl group at the 2-position of the 3-morpholinone was the most effective modification for inhibiting micro- and m-calpai...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2003.09.031

    authors: Nakamura M,Miyashita H,Yamaguchi M,Shirasaki Y,Nakamura Y,Inoue J

    更新日期:2003-12-01 00:00:00

  • Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of dibenzofluorene derivatives.

    abstract::Highly regioselective electrophilic substitution of dibenzofluorene was achieved and the nitro derivative was transformed to a variety of new anticancer agents. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00213-3

    authors: Becker FF,Mukhopadhyay C,Hackfeld L,Banik I,Banik BK

    更新日期:2000-12-01 00:00:00

  • t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.

    abstract::A series of 2-substituted 6-t-butylpyridine and 4-t-butylphenyl C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1 antagonism. The analysis of structure activity relationships indicated that the pyridine derivatives generally exhibited a little better antagonism than ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.03.004

    authors: Lee S,Kang DW,Ryu H,Kim C,Ann J,Lee H,Kim E,Hong S,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

    更新日期:2017-04-15 00:00:00

  • Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.

    abstract::This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.07.064

    authors: Evangelista W,Weir RL,Ellingson SR,Harris JB,Kapoor K,Smith JC,Baudry J

    更新日期:2016-10-15 00:00:00

  • Hypericins and thioredoxin reductase: Biochemical and docking studies disclose the molecular basis for effective inhibition by naphthodianthrones.

    abstract::Cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases experience pronounced concentration- and time-dependent inhibition when incubated with the two naphthodianthrones hypericin and pseudohypericin. Pseudohypericin turned out to be a quite strong inhibitor of TrxR1 (IC(50)=4.40μM) being far more effective...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.10.045

    authors: Sorrentino F,Karioti A,Gratteri P,Rigobello MP,Scutari G,Messori L,Bindoli A,Chioccioli M,Gabbiani C,Bergonzi MC,Bilia AR

    更新日期:2011-01-01 00:00:00

  • SAR studies of acidic dual γ-secretase/PPARγ modulators.

    abstract::A novel set of dual γ-secretase/PPARγ modulators characterized by a 2-benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the variation of the substitution pattern of the central benzene. Finally, we obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid derivatives, which act ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.08.003

    authors: Hieke M,Ness J,Steri R,Greiner C,Werz O,Schubert-Zsilavecz M,Weggen S,Zettl H

    更新日期:2011-09-15 00:00:00

  • Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their structure-anti-mycobacterial activities.

    abstract::The preparation of novel 5-aryl-2-thio-1,3,4-oxadiazoles 4a-41 and the computer-aided study of their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) are reported. The average accuracy of the electronic-topological method and neural network methods applied to the activity predict...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.05.011

    authors: Macaev F,Rusu G,Pogrebnoi S,Gudima A,Stingaci E,Vlad L,Shvets N,Kandemirli F,Dimoglo A,Reynolds R

    更新日期:2005-08-15 00:00:00

  • Oligomers of glycamino acid.

    abstract::Glycamino acids, a family of sugar amino acids, are derivatives of C-glycosides that possesses a carboxyl group at the C-1 position and an amino group replacing one of the hydroxyl groups at either the C-2, 3, 4, or 6 position. We have prepared a series of glucose-type glycamino acids as monomeric building blocks: the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00020-2

    authors: Suhara Y,Yamaguchi Y,Collins B,Schnaar RL,Yanagishita M,Hildreth JE,Shimada I,Ichikawa Y

    更新日期:2002-06-01 00:00:00

  • Design, synthesis, and binding of homologated truncated 4'-thioadenosine derivatives at the human A3 adenosine receptors.

    abstract::We synthesized homologated truncated 4'-thioadenosine analogues 3 in which a methylene (CH(2)) group was inserted in place of the glycosidic bond of a potent and selective A(3) adenosine receptor antagonist 2. The analogues were designed to induce maximum binding interaction in the binding site of the A(3) adenosine r...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.08.018

    authors: Lee HW,Kim HO,Choi WJ,Choi S,Lee JH,Park SG,Yoo L,Jacobson KA,Jeong LS

    更新日期:2010-10-01 00:00:00

  • Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3.

    abstract::A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3 was designed, synthesized and evaluated for anticonvulsant activity in rodent models of seizures: maximal electroshock (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and 6-Hz test. There...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.11.014

    authors: Gunia-Krzyżak A,Żelaszczyk D,Rapacz A,Żesławska E,Waszkielewicz AM,Pańczyk K,Słoczyńska K,Pękala E,Nitek W,Filipek B,Marona H

    更新日期:2017-01-15 00:00:00

  • Aromatic radiofluorination and biological evaluation of 2-aryl-6-[18F]fluorobenzothiazoles as a potential positron emission tomography imaging probe for β-amyloid plaques.

    abstract::To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in rad...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.03.029

    authors: Lee BC,Kim JS,Kim BS,Son JY,Hong SK,Park HS,Moon BS,Jung JH,Jeong JM,Kim SE

    更新日期:2011-05-01 00:00:00

  • Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells.

    abstract::Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential thera...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.09.010

    authors: Draoui N,Schicke O,Fernandes A,Drozak X,Nahra F,Dumont A,Douxfils J,Hermans E,Dogné JM,Corbau R,Marchand A,Chaltin P,Sonveaux P,Feron O,Riant O

    更新日期:2013-11-15 00:00:00

  • Structure-activity correlations for beta-phenethylamines at human trace amine receptor 1.

    abstract::A cell line in which RD-HGA16 cells were stably transfected with the hTAAR 1 receptor was created and utilized to carry out a systematic evaluation of a series of beta-phenethylamines. Fair agreement was observed with data obtained for aryl and ethylene chain substituted analogs in an AV12-664 cell line in which hemag...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.06.009

    authors: Lewin AH,Navarro HA,Mascarella SW

    更新日期:2008-08-01 00:00:00

  • Protective effect of ε-viniferin on β-amyloid peptide aggregation investigated by electrospray ionization mass spectrometry.

    abstract::Abnormal β-amyloid peptide accumulation and aggregation is considered to be responsible for the formation and cerebral deposition of senile plaques in the brains of patients with Alzheimer's disease (AD). Inhibition of the formation of β-amyloid (Aβ) fibrils would be an attractive therapeutic target for the treatment ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.04.001

    authors: Richard T,Poupard P,Nassra M,Papastamoulis Y,Iglésias ML,Krisa S,Waffo-Teguo P,Mérillon JM,Monti JP

    更新日期:2011-05-15 00:00:00

  • Exploiting the human peptidome for novel antimicrobial and anticancer agents.

    abstract::Infectious diseases and cancers are leading causes of death and pose major challenges to public health. The human peptidome encompasses millions of compounds that display an enormous structural and functional diversity and represents an excellent source for the discovery of endogenous agents with antimicrobial and/or ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.bmc.2017.10.038

    authors: Bosso M,Ständker L,Kirchhoff F,Münch J

    更新日期:2018-06-01 00:00:00

  • Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa.

    abstract::A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene sub...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.12.019

    authors: Kochanny MJ,Adler M,Ewing J,Griedel BD,Ho E,Karanjawala R,Lee W,Lentz D,Liang AM,Morrissey MM,Phillips GB,Post J,Sacchi KL,Sakata ST,Subramanyam B,Vergona R,Walters J,White KA,Whitlow M,Ye B,Zhao Z,Shaw KJ

    更新日期:2007-03-01 00:00:00