Characterization of a new compound, S35b, as a guanylate cyclase activator in human platelets

Ghigo, Dario; Calvino, R.; Heller, Regine; Alessio, P.; Fruttero, Roberta; Gasco, Alberto; Bosìa, Amalia; Pescarmona, Gianpiero

doi:10.1016/0006-2952(92)90504-c

Cited by 38 publications

(17 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We demonstrated that 1,1-dinitro-ethyl and 4-R-3-(Rsulphonyl)furoxans possess features characteristic of NO, i.e. they induce vasodilatation and inhibition of platelet aggregation (Ghigo et al, 1992;Gasco et al, 1993;Civelli et al, 1994).…”

Section: Introductionmentioning

confidence: 91%

The involvement of the release of nitric oxide in the pharmacological activity of the new furoxan derivative CHF 2363

Civelli¹,

Giossi²,

Caruso³

et al. 1996

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

The mechanism of action and the pharmacological effects of the new furoxan derivative, CHF 2363 (4‐ethoxy‐3‐phenylsulphonylfuroxan), were investigated. Pre‐incubation of CHF 2363 with human platelet‐rich plasma produced a concentration‐dependent inhibition of the platelet aggregation induced by collagen, adenosine diphosphate (ADP) and platelet activating factor (PAF). The test compound was about 5 times more potent than sodium nitroprusside. 3‐Isobutyl‐1‐methyl‐xanthine (IBMX) potentiated the antiaggregating effect of CHF 2363. CHF 2363 was a potent inhibitor of rubbed endothelium rabbit aortic ring contraction induced by noradrenaline. Comparison of IC50 values showed that CHF 2363 was as potent as glyceryl trinitrate (GTN). Increasing concentrations of CHF 2363 elevated platelet guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) levels. Adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) levels were unaffected. Oxyhaemoglobin reduced all the pharmacological actions of the test compound. Moreover, CHF 2363 concentration‐dependently released nitric oxide (NO) in platelet‐rich plasma. The NO release was correlated to its ability to increase platelet cyclic GMP levels. After exposure of rat aortic strips to supramaximal concentrations of GTN (550 μm), the vasorelaxant activity of CHF 2363 did not change, although that of GTN decreased about 55 fold. It has been concluded that the new furoxan derivative CHF 2363 exerts a potent antiaggregating and vasorelaxant activity via NO release and increase of cyclic GMP levels. No in vitro cross tolerance between GTN and CHF 2363 was observed.

show abstract

Section: Introductionmentioning

confidence: 91%

The involvement of the release of nitric oxide in the pharmacological activity of the new furoxan derivative CHF 2363

Civelli¹,

Giossi²,

Caruso³

et al. 1996

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Early reports showing that furoxan derivatives can mimic some of physiological actions of nitric oxide relate to the in vitro antiaggregatory and vasodilating activity of a series of isomer methyl-arylsulfonylfuroxans [7,8]. 4-Methyl-3-phenylsulfonylfuroxan (1), one of the most active products of the series, has been closely examined for its biochemical pharmacology [9]. It showed typical behavior of a NO donor.…”

Section: Furoxans As No Donorsmentioning

confidence: 99%

NO donors: Focus on furoxan derivatives

Gasco

Fruttero

Sorba

et al. 2004

Pure and Applied Chemistry

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Recently, we described a new class of compounds, with a furoxan structure, which have been shown to possess NOmimetic pharmacological activities Ghigo et al, 1992). The mechanism of action of furoxancarboxamides at the molecular level has been investigated by Feelisch et al (1992) who found that these compounds react with sulphydryl groups of low molecular weight thiols and proteins.…”

Section: Introductionmentioning

confidence: 99%

A new class of furoxan derivatives as NO donors: mechanism of action and biological activity

Ferioli

Folco

Ferretti

et al. 1995

British J Pharmacology

View full text Add to dashboard Cite

1 The mechanism of action and biological activity of a series of R-substituted and di-R-substituted phenylfuroxans is reported. 2 Maximal potency as vasodilators on rabbit aortic rings, precontracted with noradrenaline (1 pM), was shown by phenyl-cyano isomers and by the 3,4-dicyanofuroxan, characterized by a potency ratio 3-10 fold higher than glyceryl trinitrate (GTN). This effect was reduced upon coincubation with methylene blue or oxyhaemoglobin (10 gLM). 3 The furoxan derivatives showing maximal potency as vasodilators were also able to inhibit collageninduced platelet aggregation, with ICW values in the sub-micromolar range. 4 The furoxan derivatives were able to stimulate partially purified, rat lung soluble guanylate cyclase; among the most active compounds, the 3-R-substituted isomers displayed a higher level of stimulatory effect than the 4-R analogues. 5 Solutions (O.1 mM) of all the tested furoxans, prepared using 50 mM phosphate buffer, pH 7.4, (diluting 1O mM DMSO stock solutions) did not release nitric oxide (NO) spontaneously; however in presence of 5 mM L-cysteine, a significant NO-releasing capacity was observed, which correlated significantly with their stimulation of the guanylate cyclase activity.

show abstract

Characterization of a new compound, S35b, as a guanylate cyclase activator in human platelets

Cited by 38 publications

References 35 publications

The involvement of the release of nitric oxide in the pharmacological activity of the new furoxan derivative CHF 2363

The involvement of the release of nitric oxide in the pharmacological activity of the new furoxan derivative CHF 2363

NO donors: Focus on furoxan derivatives

A new class of furoxan derivatives as NO donors: mechanism of action and biological activity

Contact Info

Product

Resources

About