Synthesis and Pharmacological Characterization of New H2-Antagonists Containing NO-Donor Moieties, Endowed with Mixed Antisecretory and Gastroprotective Activities

Bertinaria, Massimo; Sorba, Giovanni; Medana, Claudio; Cena, Clara; Adami, Maristella; Morini, Giuseppina; Pozzoli, Cristina; Coruzzi, Gabriella; Gasco, Alberto

doi:10.1002/(sici)1522-2675(20000119)83:1<287::aid-hlca287>3.0.co;2-2

Cited by 17 publications

(8 citation statements)

References 20 publications

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“…Finally, using the moderate NO donor 3-carbamoylfuroxan-4-yloxymethyl group, this second curve was only partially shifted rightwards, and consequently the resulting product 3 displayed vasodilatory activity dependent both on its calcium channel blocker and its NO donor properties, in a wide range of concentrations. A similar strategy was followed to balance in vivo a series of NO donor H 2 -antagonists [22]. These products were designed to produce new H 2 -antagonists endowed with gastroprotective properties dependent on their ability to release NO.…”

Section: Furoxan/drug Hybridsmentioning

confidence: 99%

NO donors: Focus on furoxan derivatives

Gasco

Fruttero

Sorba

et al. 2004

Pure and Applied Chemistry

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Abstract:The article focuses attention on furoxan derivatives (1,2,5-oxadiazole 2-oxides) as NO donors. Possible mechanisms for NO release from these products in physiological solution and in segments of rabbit femoral artery are briefly considered. The in vitro antiaggregatory activities and the in vitro and in vivo vasodilating properties of a number of furoxans are examined with particular reference to involvement of NO in these actions. The use of the furoxan system to design new NO donor/drug hybrids is discussed in connection with the problem of the balance between NO-and drug-dependent activities of the resulting structures. Whether other biological activities (as yet, little studied) of furoxans, such as their antiparasite, antimicrobial, and antitumoral effects, are NO-dependent, is a matter still to be explored.

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Section: Furoxan/drug Hybridsmentioning

confidence: 99%

NO donors: Focus on furoxan derivatives

Gasco

Fruttero

Sorba

et al. 2004

Pure and Applied Chemistry

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“…Our research group has been active in this field and we have designed several such products 1. These compounds include NO‐donor nonsteroidal antiinflammatory drugs (NSAIDs)4, 5 and NO‐donor H 2 ‐receptor antagonists 6. We pursued this line because nitric oxide (NO . )…”

Section: Methodsmentioning

confidence: 99%

A New Furoxan NO‐Donor Rabeprazole Derivative and Related Compounds

Sorba¹,

Galli²,

Cena³

et al. 2003

ChemBioChem

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Stomach pump: Gastric antisecretory and protective activity against damaging agents are shown by the pump inhibitor rabeprazole (1). This compound is also potently active against Helicobacter pylori strains that are resistant to metronidazole. Modification of 1 with a furazan or furoxan group significantly reduced its antisecretory potency but not its efficacy. The furoxan analogue, which can act as an NO donor, has a protective activity comparable to that of the parent molecule.

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“…NO donation by furoxan is presumed to be mediated by a reactive/nucleophilic thiol attack on the compound followed by a molecular rearrangement that ultimately releases a single equivalent of NO (several mechanisms have been postulated). With the current understanding of the biochemical effects of NO, this chemotype has entered into studies of β 2 -adrenoceptor agonism, within aspirin conjugates for platelet aggregation inhibition and as H 2 -receptor antagonists [48–50]. Based upon this known activity, we examined the release of NO from furoxan following a single 10 μM exposure to 15 nM S. mansoni TGR in the presence of NADPH.…”

Section: Inhibitors Of Thioredoxin Glutatione Reducatasementioning

confidence: 99%

The Pilot Phase of the NIH Chemical Genomics Center

Thomas

Auld²,

Huang³

et al. 2009

CTMC

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The NIH Chemical Genomics Center (NCGC) was the inaugural center of the Molecular Libraries and Screening Center Network (MLSCN). Along with the nine other research centers of the MLSCN, the NCGC was established with a primary goal of bringing industrial technology and experience to empower the scientific community with small molecule compounds for use in their research. We intend this review to serve as 1) an introduction to the NCGC standard operating procedures, 2) an overview of several of the lessons learned during the pilot phase and 3) a review of several of the innovative discoveries reported during the pilot phase of the MLSCN. High-throughput screening at the NCGCHigh-throughput screening (HTS) is one of the most established mechanisms to identify small molecules with biological activity [1]. The model of the Molecular Libraries and Screening Center Network (MLSCN) provides researchers that have established assays for either isolated targets or cellular phenotypes the resources to conduct a HTS for small molecules that affect that target or phenotype [2]. HTS has evolved to address a wide-range of biological functions by employing a multitude of formats that now includes assays for purified proteins and enzymes as well as cell-based assays for signal transduction pathways, protein complex formation, transcriptional regulation of gene function, pre-mRNA splicing events, and epigenetics [3]. The NIH Chemical Genomics Center (NCGC) has established a number of innovations aimed at reducing the burden of false positives (FP) and false negatives (FN) associated with HTS as well as providing efficient use of assay reagents and compound samples. Primary among these innovations is the establishment of multi-concentration HTS using miniaturized assay volumes (<10 μL/well) in 1536-well microtiter plates, referred to as quantitative high-throughput screening (qHTS) [4]. qHTS is capable of screening small molecules at multiple concentrations (typically between 7 and 15 specified concentrations) based upon the built-in flexibility of inter-plate titrations (Fig. 1). By miniaturizing to a 1536 well-plate format the qHTS process essentially provides cost-effective high-throughput pharmacology by delivering concentration response curves (CRCs) for each library member. The benefits of qHTS include reducing FP and capturing FN, allowing the data to be mined to determine a compound's pharmacological profile, the ability to identify assay related artifacts, and the ability to construct structure activity relationships (SAR) from the primary screening data to drive probe optimization immediately after completion of the screen. The NCGC has applied qHTS to many different assay formats * Corresponding authors: craigt@nhgri.nih.gov, austinc@mail.nih.gov. Send proofs to: Dr. Craig J. Thomas, NIH Chemical Genomics Center, NHGRI, National Institutes of Health, 9800 Medical Center Drive, Building B, Room 3005, MSC: 3370, Bethesda, MD 20892-3370 NIH Public Access Author ManuscriptCurr Top Med Chem. Author manuscript; ava...

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Synthesis and Pharmacological Characterization of New H2-Antagonists Containing NO-Donor Moieties, Endowed with Mixed Antisecretory and Gastroprotective Activities

Cited by 17 publications

References 20 publications

NO donors: Focus on furoxan derivatives

NO donors: Focus on furoxan derivatives

A New Furoxan NO‐Donor Rabeprazole Derivative and Related Compounds

The Pilot Phase of the NIH Chemical Genomics Center

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