Novel small-molecule inhibitors of arylamine N-acetyltransferases: drug discovery by high-throughput screening.

Abstract:

:Arylamine N-acetyltransferases (NATs) are a family of enzymes found in eukaryotes and prokaryotes. While the precise endogenous function of NAT remains unknown for most organisms, recent evidence has shown that the expression of human NAT1 is up-regulated in estrogen receptor positive breast cancer. Additionally, NAT in mycobacteria is required for mycobacterial cell wall biosynthesis and survival of the organisms within macrophage. It is therefore important to develop small molecule inhibitors of NATs as molecular tools to study the function of NATs in various organisms. Such inhibitors may also prove useful in future drug design, for example in the development of anti tubercular agents. We describe a high-throughput screen of a proprietary library of 5016 drug-like compounds against three prokaryotic NAT enzymes and two eukaryotic NAT enzymes.

authors

Westwood IM,Kawamura A,Russell AJ,Sandy J,Davies SG,Sim E

doi

10.2174/138620711794474051

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

117-24

issue

2

eissn

1386-2073

issn

1875-5402

pii

BSP/CCHTS/E- Pub/00131

journal_volume

14

pub_type

杂志文章
  • Microwave-assisted synthesis of bioactive quinazolines and quinazolinones.

    abstract::This paper aims to review recent developments in the synthesis of quinazolines and quinazolinone derivatives under conditions that include the application of microwave heating in the ring forming step. Recently, two reviews on the synthesis and chemistry of natural and synthetic quinazolines and quinazolinones have be...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章,评审

    doi:10.2174/138620707783220356

    authors: Besson T,Chosson E

    更新日期:2007-12-01 00:00:00

  • A collaborative hit-to-lead investigation leveraging medicinal chemistry expertise with high throughput library design, synthesis and purification capabilities.

    abstract::High throughput screening (HTS) campaigns, where laboratory automation is used to expose biological targets to large numbers of materials from corporate compound collections, have become commonplace within the lead generation phase of pharmaceutical discovery. Advances in genomics and related fields have afforded a we...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/138620706775541891

    authors: Yang X,Parker D,Whitehead L,Ryder NS,Weidmann B,Stabile-Harris M,Kizer D,McKinnon M,Smellie A,Powers D

    更新日期:2006-02-01 00:00:00

  • Scutellaria barbata flavonoids improve the composited Aβ-induced abnormal changes of glial cells in rats' brain.

    abstract:AIM:It has been reported that glial cells are involved in Alzheimer's disease (AD). According to our previous research, Scutellaria barbata flavonoids (SBFs) can protect the neuronal disorder and memory impairment for AD-like rats, while the effect of SBFs on the glial cells disorder in AD-like rats has been less well ...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666201209092358

    authors: Cheng JJ,Guo Q,Wu XG,Ma S,Gao Y,Ya-Zhen S

    更新日期:2020-12-08 00:00:00

  • The role of in vitro ADME assays in antimalarial drug discovery and development.

    abstract::The high level of attrition of drugs in clinical development has led pharmaceutical companies to increase the efficiency of their lead identification and development through techniques such as combinatorial chemistry and high-throughput (HTP) screening. Since the major reasons for clinical drug candidate failure other...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章,评审

    doi:10.2174/1386207053328129

    authors: Shearer TW,Smith KS,Diaz D,Asher C,Ramirez J

    更新日期:2005-02-01 00:00:00

  • Emerging analytical separation techniques with high throughput potential for pharmaceutical analysis, part I: Stationary phase and instrumental developments in LC.

    abstract::In recent years, a trend of change has been observed within pharmaceutical industry. As modern drug discovery has reached a remarkable level of complexity and drugs need to be discovered, developed and produced against strict timelines and within cost- and regulatory constraints, industry seeks "lean" solutions to inc...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章,评审

    doi:10.2174/138620710791515897

    authors: Pieters S,Dejaegher B,Vander Heyden Y

    更新日期:2010-07-01 00:00:00

  • Insight into the structural requirements of narlaprevir-type inhibitors of NS3/NS4A protease based on HQSAR and molecular field analyses.

    abstract::In the life cycle of hepatitis C virus (HCV), NS3/NS4A protease has been proved to play a vital role in the replication of the HCV virus. Narlaprevir and its derivatives, the inhibitors of NS3/NS4A, would be potentially developed as important anti-HCV drugs in the future. In this study, quantitative structure-activity...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/138620712800563918

    authors: Zhu J,Li Y,Yu H,Zhang L,Mao X,Hou T

    更新日期:2012-07-01 00:00:00

  • 3D QSAR and docking study of gliptin derivatives as DPP-IV inhibitors.

    abstract::The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 46 xanthine derivatives reported for DPP-IV inhibition using PHASE module of Schrodinger software. The present works also encompasses molecular interaction of 46 xanthine ligand th...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207311316040001

    authors: Agrawal R,Jain P,Dikshit SN,Bahare RS

    更新日期:2013-05-01 00:00:00

  • Resisting the Resistance in Cancer: Cheminformatics Studies on Short- Path Base Excision Repair Pathway Antagonists Using Supervised Learning Approaches.

    abstract::Survival of cells and maintenance of genome depend on detection and repair of damaged DNA through intricate mechanisms. Cancer treatment relies on chemotherapy or radiation therapy that kills neoplastic cells by causing immense damage to the DNA. In many cases, escalated DNA repair mechanism leads to resistance agains...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207318666150626093648

    authors: Jain R,Jamal S,Goyal S,Wahi D,Singh A,Grover A

    更新日期:2015-01-01 00:00:00

  • Suzuki-Miyaura and Stille reactions as key steps in the synthesis of diversely functionalized Amaryllidaceae alkaloid analogs bearing a 5,6,7,8-tetrahydrobenzo[c,e]azocine skeleton.

    abstract::Microwave-assisted Suzuki-Miyaura and Stille cross-coupling reactions for the synthesis of highly electron-rich and diversely functionalized biaryl intermediates are presented. Microwave-irradiation has been demonstrated to be a very powerful tool for performing difficult transition metal-catalyzed cross-coupling reac...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/138620707783018513

    authors: Appukkuttan P,Dehaen W,Van der Eycken E

    更新日期:2007-11-01 00:00:00

  • Caffeic Acid in Dermatological Formulations: In Vitro Release Profile and Skin Absorption.

    abstract:AIM AND OBJECTIVE:Caffeic acid (CA) is a cinnamic acid derivative, found in many vegetable products, with powerful antioxidant activity, the ability to increase collagen production and capacity to prevent premature aging of the skin. The classic emulsions of CA are widely used by the consumer to provide a pleasant, ref...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207320666170602090448

    authors: Spagnol CM,Di Filippo LD,Isaac VLB,Correa MA,Salgado HRN

    更新日期:2017-01-01 00:00:00

  • Scaffold hopping for identification of novel PKCβII inhibitors based on ligand and structural approaches, virtual screening and molecular dynamics study.

    abstract::Protein Kinase C βII (PKCβII) overexpression has been linked to various diabetic microvascular complications viz. retinopathy, neuropathy, and cardiomyopathy. Novel and potent small molecules with preferential selective inhibitory property of PKCβII will be helpful in treatment as well as understanding insight of PKCβ...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207311301010008

    authors: Grewal BK,Sobhia ME

    更新日期:2014-01-01 00:00:00

  • New Ca2+ fluoroionophores based on the BODIPY fluorophore.

    abstract::Calcium (Ca(2+)) fluoroionophores are useful in cell-based functional assays of G-protein coupled receptor (GPCR) activation or ion channel modulation. In this paper we describe new calcium probes that improve or overcome certain deficiencies in existing probes. These new fluoroionophores are based on acylation of ami...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/138620703106298455

    authors: Gee KR,Rukavishnikov A,Rothe A

    更新日期:2003-06-01 00:00:00

  • A high-throughput mammalian protein expression, purification, aliquoting and storage pipeline to assemble a library of the human secretome.

    abstract::In the post-human genome-sequencing era, the availability of recombinant proteins has become crucial for the identification of proteins with therapeutic potential. Based upon bioinformatic coding predictions of the genes for putative secreted proteins, we established a high-throughput protein pipeline (HTPP) for the p...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/138620706778700143

    authors: Battle T,Antonsson B,Feger G,Besson D

    更新日期:2006-11-01 00:00:00

  • A green and efficient protocol for the synthesis of quinoxaline, benzoxazole and benzimidazole derivatives using heteropolyanion-based ionic liquids: as a recyclable solid catalyst.

    abstract::In this paper, we introduce two nonconventional ionic liquid compounds which are composed of propane sulfonate functionalized organic cations and heteropolyanions as green solid acid catalysts for the highly efficient and green synthesis of 2,3-disubstitutedquinoxaline derivatives. These ionic liquids are in the solid...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207311316080004

    authors: Vahdat SM,Baghery S

    更新日期:2013-09-01 00:00:00

  • Gene expression analysis for high throughput screening applications.

    abstract::To meet growing needs for high throughput gene expression profiling, we established a new automated high throughput TaqMan RT-PCR method for quantitative mRNA expression analysis. In this method, the Allegro( trade mark ) (Zymark) system conducts all sample tracking and liquid handling steps, and ABI PRISM 7900 HT (Ap...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/138620704773120810

    authors: Pinhasov A,Mei J,Amaratunga D,Amato FA,Lu H,Kauffman J,Xin H,Brenneman DE,Johnson DL,Andrade-Gordon P,Ilyin SE

    更新日期:2004-03-01 00:00:00

  • Metalloproteinase inhibitors for the disintegrin-like metalloproteinases ADAM10 and ADAM17 that differentially block constitutive and phorbol ester-inducible shedding of cell surface molecules.

    abstract::The transmembrane metzinkin-proteases of the ADAM (a disintegrin and a metalloproteinase)-family ADAM10 and ADAM 17 are both implicated in the ectodomain shedding of various cell surface molecules including the IL6-receptor and the transmembrane chemokines CX3CL1 and CXCL16. These molecules are constitutively released...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章,评审

    doi:10.2174/1386207053258488

    authors: Ludwig A,Hundhausen C,Lambert MH,Broadway N,Andrews RC,Bickett DM,Leesnitzer MA,Becherer JD

    更新日期:2005-03-01 00:00:00

  • Moringa oleifera leaf extract attenuates Pb acetate-induced testicular damage in rats.

    abstract:BACKGROUND:Lead (Pb) remains a common contaminant in the environment in many parts of the world. Pb exposure adversely affects many human organs, including the gonads, via oxidant and inflammatory marker propagation in affected tissues. Moringa oleifera leaf extract (MOE) is a rich source of antioxidants reported to ha...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666200923142831

    authors: Albasher G,Alrajhi R,Alshammry E,Almeer R

    更新日期:2020-09-23 00:00:00

  • Novel Thiazole-Based Thiazolidinones as Potent Anti-infective Agents: In silico PASS and Toxicity Prediction, Synthesis, Biological Evaluation and Molecular Modelling.

    abstract:AIMS AND OBJECTIVE:The infectious disease treatment remains a challenging concern owing to the increasing number of pathogenic microorganisms associated with resistance to multiple drugs. A promising approach for combating microbial infection is to combine two or more known bioactive heterocyclic pharmacophores in one ...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666200127115238

    authors: Tratrat C

    更新日期:2020-01-01 00:00:00

  • Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats.

    abstract:AIM AND OBJECTIVE:The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on "nourish yin". However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has ...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666200407080352

    authors: Li LZ,Lei SS,Li B,Zhou FC,Chen YH,Su J,Lv GY,Chen SH

    更新日期:2020-01-01 00:00:00

  • Correlative Study of Bone-Related Biochemicals and Endocrine Changes in Perimenopausal Women in Enugu, Nigeria.

    abstract:BACKGROUND AND OBJECTIVE:Perimenopause is a physiological occurrence in women, and is characterized by endocrine and biochemical changes. During perimenopause phase, many derangements or abnormal health conditions start developing as a result of hormonal changes. These derangements in health conditions and biochemical ...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666201023120212

    authors: Ikegwuonu CI,Uchendu IK,Maduka CI

    更新日期:2020-10-23 00:00:00

  • Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform.

    abstract:AIM AND OBJECTIVE:Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. MAT...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207322666190412165316

    authors: Ivanenkov YA,Yamidanov RS,Osterman IA,Sergiev PV,Aladinskiy VA,Aladinskaya AV,Terentiev VA,Veselov MS,Ayginin AA,Skvortsov DA,Komarova KS,Chemeris AV,Baimiev AK,Sofronova AA,Malyshev AS,Machulkin AE,Petrov RA,Bezrukov D

    更新日期:2019-08-08 00:00:00

  • Target identification strategies in chemical genetics.

    abstract::Chemical inhibitors have had a profound impact on many diverse fields of biology. The goal of chemical genetics is to use small molecules to perturb biological systems in a manner conceptually similar to traditional genetics. Key to the advancement of the chemical genetic paradigm is the further development of tools a...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章,评审

    doi:10.2174/1386207043328391

    authors: Tochtrop GP,King RW

    更新日期:2004-11-01 00:00:00

  • Exploration of the Potential Mechanism of Calculus Bovis in Treatment of Primary Liver Cancer by Network Pharmacology.

    abstract:AIM AND OBJECTIVE:Calculus Bovis (CB) has been employed to treat diseases for a long time. It has been identified to play significant anti-inflammatory and anti-tumor roles. However, the mechanism of treating primary liver cancer (PLC) remains to be revealed. This study aims to clarify the molecules and mechanisms of C...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666200808172051

    authors: Zhang Z,Zeng P,Gao W,Wu R,Deng T,Chen S,Tian X

    更新日期:2021-01-01 00:00:00

  • Mechanistic Insights to the Binding of Antibody CR3022 Against RBD from SARS-CoV and HCoV-19/SARS-CoV-2: A Computational Study.

    abstract:Aims & Objective:Corona Virus Disease 2019 (COVID-19) caused by the human coronavirus 2019 (HCoV-19, also known as SARS-CoV-2) infection is currently in a global outbreak. COVID-19 has posed a huge threat to public health and economic stability worldwide. CR3022, a human monoclonal neutralizing antibody isolated from a...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666201026160500

    authors: Yu W,Wu X,Ren J,Zhang X,Wang Y,Li C,Xu W,Li J,Li G,Zheng W,Liao H,Yuan X

    更新日期:2020-10-26 00:00:00

  • High-throughput tools for the study of protein-nanostructured surface interaction.

    abstract::The aim of this review is to describe and to analyze the ingredients that are necessary in order to develop a robust and effective experimental approach for the high-throughput characterization of protein-nanostructured surface interaction. In the first part of this paper we review the nanostructured surface synthesis...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章,评审

    doi:

    authors: Scopelliti PE,Bongiorno G,Milani P

    更新日期:2011-03-01 00:00:00

  • Evaluation of drug transporter interactions in drug discovery and development.

    abstract::Drug transporters play an important role in the absorption, distribution, excretion and toxicity of both endogenous and exogenous compounds. Transporters may act as physiological 'gatekeepers' in the regulation of the pharmacological and/or toxicological effects of drugs by limiting distribution to tissues responsible...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章,评审

    doi:10.2174/138620710790596772

    authors: Lai Y,Sampson KE,Stevens JC

    更新日期:2010-02-01 00:00:00

  • Identification of Three Differentially Expressed miRNAs as Potential Biomarkers for Lung Adenocarcinoma Prognosis.

    abstract:OBJECTIVE:The aim of this study areto screen MicroRNAs (miRNAs) related to the prognosis of lung adenocarcinoma (LUAD) and to explore the possible molecular mechanisms. METHODS:The data for a total of 535 patients with LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database. The miRNAs for LUAD prognosi...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207323666200124123103

    authors: Wang W,Liu B,Duan X,Feng X,Wang T,Wang P,Ding M,Zhang Q,Feng F,Wu Y,Yao W,Wang Q,Yang Y

    更新日期:2020-01-01 00:00:00

  • Time-resolved fluorescence measurements using microlens array and area imaging devices.

    abstract::Time-resolved fluorescence (TRF) assay formats are frequently used technologies in high-throughput screening. In this article, we have characterised the novel Plate::Vision(2) 96-microlens array reader (Carl Zeiss Jena GmbH, Germany) and compared it to the novel LEADseeker Generation IV multimodality imaging system (L...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/138620704772884814

    authors: Merk S,Lietz A,Kroner M,Valler M,Heilker R

    更新日期:2004-02-01 00:00:00

  • Efficient One-Pot Synthesis of Thiazol-2-imine Derivatives through Regioselective Reaction Between Primary Amines, Phenylisothiocyanate, and α-Chloroacetaldehyde.

    abstract:AIM AND OBJECTIVE:Thiazol-2-imine derivatives are interested for their pharmaceutical and biologic activities. A literature survey reveals that there have been no any reports on the synthesis of thiazol-2-imine derivatives without substituents in position C-4 and C-5 via one-pot reaction. Herein we report an efficient ...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1568009617666161107093942

    authors: Nasiri F,Sabahi-Agabager L

    更新日期:2017-01-01 00:00:00

  • Streamlined in vivo selection and screening of human prostate carcinoma avid phage particles for development of peptide based in vivo tumor imaging agents.

    abstract::Bacteriophage (phage) display has been exploited for the purpose of discovering new cancer specific targeting peptides. However, this approach has resulted in only a small number of tumor targeting peptides useful as in vivo imaging agents. We hypothesize that in vivo screening for tumor uptake of fluorescently tagged...

    journal_title:Combinatorial chemistry & high throughput screening

    pub_type: 杂志文章

    doi:10.2174/1386207311107010009

    authors: Newton-Northup JR,Figueroa SD,Deutscher SL

    更新日期:2011-01-01 00:00:00