Mechanistic differences between in vitro assays for hydrazone-based small molecule inhibitors of anthrax lethal factor

Hanna, M.Leslie; Tarasow, Theodore M.; Perkins, Julie

doi:10.1016/j.bioorg.2006.07.004

Cited by 23 publications

(23 citation statements)

References 25 publications

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“…The LF inhibitors identified thus far contain key Zn 2+ -chelating moieties7 such as a hydroxymate8–13, polyphenols/catechol14,15, penicillin based16, rhodanine17,18,14,6,19, aminoglycoside20–22, quinoline urea23, and hydrazone24,25. In this study, we present the identification of a novel scaffold shown to inhibit LF in vitro and in cell .…”

Section: Resultsmentioning

confidence: 95%

Structure–activity relationship studies of a novel series of anthrax lethal factor inhibitors

Johnson

Chen

Barile

et al. 2009

Bioorganic & Medicinal Chemistry

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We report on the identification of a novel small molecule inhibitor of anthrax lethal factor using a high-throughput screening approach. Guided by molecular docking studies, we carried out structure activity relationship (SAR) studies and evaluated activity and selectivity of most promising compounds in in vitro enzyme inhibition assays and cellular assays. Selected compounds were further analyzed for their in vitro ADME properties, which allowed us to select two compounds for further preliminary in vivo efficacy studies. The data provided represents the basis for further pharmacology and medicinal chemistry optimizations that could result in novel anti-Anthrax therapies.

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Section: Resultsmentioning

confidence: 95%

Structure–activity relationship studies of a novel series of anthrax lethal factor inhibitors

Johnson

Chen

Barile

et al. 2009

Bioorganic & Medicinal Chemistry

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“…Antiplatelets decrease platelet aggregation and prevent the formation of thrombus. Hydrazone derivatives (15,16,17) exhibited an in vitro antiplatelet activity; see Figure 3.…”

Section: Antiplatelet Activitymentioning

confidence: 99%

“…A series of hydrazones were evaluated as potential inhibitors of anthrax lethal factor. There were significant differences in the types of inhibition observed with the different assays [17]. Kinetic analysis of the dipeptidyl disulfides and dipeptidyl benzoylhydrazones indicated that these inhibitors act as irreversible inhibitors of Cathepsin S, and benzoylhydrazones were shown to be potent inhibitors of Cathepsin S [18].…”

Section: Introductionmentioning

confidence: 98%

Analgesic, Anti-Inflammatory, and Antiplatelet Profile of Hydrazones Containing Synthetic Molecules

Asif

Husain

2013

Journal of Applied Chemistry

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Hydrazones are present in many of the bioactive compounds with wide interest because of their diverse pharmacological applications. Hydrazones possess wide variety of biological activities such as anticonvulsant, antidepressant, analgesic, anti-inflammatory, antiplatelet, antimicrobial, anticancer, antihypertensive, anthelmintic, antidiabetic, antiparasitic, and other anticipated activities. This created an interest for researchers towards synthesized variety of hydrazone derivatives for different biological activities. Therefore many researchers have synthesized hydrazone derivatives as target structures for their biological activities. This is paper focuses on the analgesic, anti-inflammatory, and antiplatelet activities of hydrazones.

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“…Thus, detection of cleavage was observed directly by mass spectroscopy without prior need for further purification of substrates and products. Using the hydrazone bond of DS-998, Hanna et al [58] generated a series of libraries, later analysed by in vitro assays in search for novel LFis. Using the hydrazone bond of DS-998, Hanna et al [58] generated a series of libraries, later analysed by in vitro assays in search for novel LFis.…”

Section: Hydrazone-based Moleculesmentioning

confidence: 99%

“…Using the hydrazone bond of DS-998, Hanna et al [58] generated a series of libraries, later analysed by in vitro assays in search for novel LFis. IC 50 values were in the micromolar range with similar Kis to the initial lead compound DS-998 [58]. IC 50 values were in the micromolar range with similar Kis to the initial lead compound DS-998 [58].…”

Section: Hydrazone-based Moleculesmentioning

confidence: 99%

Low Molecular Weight Inhibitors of the Protease Anthrax Lethal Factor

Δάλκας

Papakyriakou²,

Vlamis-Gardikas³

et al. 2008

MRMC

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Anthrax Lethal Factor (LF) is a zinc-dependent metalloprotease that together with the protective antigen constitute the anthrax lethal toxin, the most prominent virulence factor of the disease anthrax. This review summarizes the current knowledge on anthrax toxicity and defense in relation to LF. Particular emphasis is placed on the structural aspects of LF, the properties of its substrates and the achievements in the design of low molecular weight inhibitors of the catalytic activity of the metalloenzyme.

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Mechanistic differences between in vitro assays for hydrazone-based small molecule inhibitors of anthrax lethal factor

Cited by 23 publications

References 25 publications

Structure–activity relationship studies of a novel series of anthrax lethal factor inhibitors

Structure–activity relationship studies of a novel series of anthrax lethal factor inhibitors

Analgesic, Anti-Inflammatory, and Antiplatelet Profile of Hydrazones Containing Synthetic Molecules

Low Molecular Weight Inhibitors of the Protease Anthrax Lethal Factor

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