Barbituric Acid Derivatives as Protein Tyrosine Phosphatase Inhibitors

Kafle, Bhooshan; Bhattarai, Bharat Raj; Cho, Hyeongjin

doi:10.5012/bkcs.2011.32.1.31

Cited by 7 publications

(4 citation statements)

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“…PTP inhibitors have been investigated for effect on toxins, biofilm formation, quorum sensing, cell adhesion and type III secretion systems [17, 29-31]. PTK inhibitors are successfully used in cancer therapy [32] and PTP inhibitors are potential oncology drugs [33].…”

Section: Introductionmentioning

confidence: 99%

“…To combat increasing numbers of bacterial pathogens resistant to current drugs and the lack of anti-infective agents to treat infections with resistant phenotypes, compounds attacking virulence mechanisms have been investigated as potential therapeutic agents [ 28 ]. PTP inhibitors have been investigated for effect on toxins, biofilm formation, quorum sensing, cell adhesion and type III secretion systems [ 17 , 29 - 31 ]. PTK inhibitors are successfully used in cancer therapy [ 32 ] and PTP inhibitors are potential oncology drugs [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Nitropropenyl Benzodioxole, An Anti-Infective Agent with Action as a Protein Tyrosine Phosphatase Inhibitor

White¹,

Nicoletti²,

Borland³

2014

TOMCJ

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We report on the activities of a broad spectrum antimicrobial compound,nitropropenyl benzodioxole (NPBD) which are of relevance to its potential as an anti-infective drug. These investigations support the proposal that a major mechanism of NPBD is action as a tyrosine mimetic, competitively inhibiting bacterial and fungal protein tyrosine phosphatases (PTP).NPBD did not affect major anti-bacterial drug targets, namely, ATP production, cell wall or cell membrane integrity, or transcription and translation of RNA. NPBD inhibited bacterial YopH and human PTP1B and not human CD45 in enzyme assays. NPBD inhibited PTP-associated bacterial virulence factors, namely, endospore formation in Bacillus cereus, prodigiosin secretion in Serratia marcescens, motility in Proteus spp., and adherence and invasion of mammalian cells by Yersinia enterocolitica. NPBD acts intracellularly to inhibit the early development stages of the Chlamydia trachomatis infection cycle in mammalian cells known to involve sequestration of host cell PTPs. NPBD thus both kills pathogens and inhibits virulence factors relevant to early infection, making it a suitable candidate for development as an anti-infective agent, particularly for pathogens that enter through, or cause infections at, mucosal surfaces. Though much is yet to be understood about bacterial PTPs, they are proposed as suitable anti-infective targets and have been linked to agents similar to NPBD. The structural and functional diversity and heterogeneous distribution of PTPs across microbial species make them suitably selective targets for the development of both broadly active and pathogen-specific drugs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nitropropenyl Benzodioxole, An Anti-Infective Agent with Action as a Protein Tyrosine Phosphatase Inhibitor

White¹,

Nicoletti²,

Borland³

2014

TOMCJ

View full text Add to dashboard Cite

show abstract

“…Compound 1 exhibited a noncompetitive inhibition pattern for PTP1B and a mixed-type noncompetitive pattern for YPTP1. 3 The binding sites of the barbiturate derivatives on PTP1B and YPTP1 are yet to be determined through X-ray crystallographic study of the enzyme-inhibitor complex. However, in the present study, the barbiturate moiety was recognized as a scaffold for the design of active site-direct inhibitors of VHR phosphatase.…”

mentioning

confidence: 99%

“…4 Recently, we reported the inhibitory activities of barbiturates against protein tyrosine phosphatase (PTP) 1B and other PTPs. 3 The study focused on the barbiturates with a substituent at C-5 of a barbituric acid core structure, and compound 1 was identified as the most potent PTP1B inhibitor among the series. Commonly used barbiturates like phenobarbital and sodium pentothal have a substituent at C-5 of this basic skeleton.…”

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confidence: 99%