Water Soluble Furoxan Derivatives as NO Prodrugs

Sorba, Giovanni; Medana, Claudio; Fruttero, Roberta; Cena, Clara; Stilo, Antonella Di; Galli, Ubaldina; Gasco, Alberto

doi:10.1021/jm970281u

Cited by 32 publications

(63 citation statements)

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“…A number of water-soluble furoxans, bearing as substituent a chain containing an amino function partially protonated at physiological pH, were systematically studied for their NO-dependent vasodilating properties [13]. All these products dilate rat aorta strips precontracted with noradrenaline in a concentration-dependent manner.…”

Section: Furoxans As No Donorsmentioning

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: Furoxans As No Donorsmentioning

confidence: 99%

NO donors: Focus on furoxan derivatives

Gasco

Fruttero

Sorba

et al. 2004

Pure and Applied Chemistry

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“…The extent of NO production after 1 h was determined by detection of nitrites, which are the oxidative metabolites of nitric oxide (Griess reaction). 9 The results expressed as percentages of NO 2 -(mol/mol) are reported in Table 1.…”

Section: Introductionmentioning

confidence: 99%

New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities

et al. 1998

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A series of 4-phenyl-1,4-dihydropyridines substituted at the ortho and meta positions of the phenyl ring with NO-donating furoxan moieties and their non-NO-releasing furazan analogues were synthesized and pharmacologically characterized. The vasodilator activities of these compounds were evaluated on rat aorta and expressed as EC50 values or as EC50iGC values when obtained in the presence of inhibitors of guanylate cyclase methylene blue (MB) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Affinities to 1, 4-DHP receptors on Ca2+ channels, expressed as IC50 values, were determined through displacement experiments of [3H]nitrendipine on rat cortex homogenates. A linear correlation between IC50 and EC50 values was found for compounds unable to release NO. EC50calcd values for derivatives containing NO-donor moieties, expression of the Ca2+-blocking component of their vasodilator activity, were interpolated on this linear regression. They showed a good correspondence with EC50iGC values determined in the presence of soluble guanylate cyclase inhibitors. Analysis of EC50iGC/EC50 ratios provided a useful tool to distinguish well-balanced hybrids from derivatives biased toward Ca2+-blocking or NO-dependent vasodilator activity. A detrimental effect on affinity to the 1, 4-DHP receptor, due to substitution at the ortho and meta positions of the 4-phenyl ring, was observed. SAR to explain this effect is proposed.

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“…Nitrites are the most-important products of the oxidation of NO in aerobic aqueous solution. They were detected by the Griess reaction according to a procedure we had previously used [23]. The results are collected in Table 1.…”

Section: Methodsmentioning

confidence: 99%

The Furoxan System: Design of Selective Nitric Oxide (NO) Donor Inhibitors of COX-2 Endowed with Anti-Aggregatory and Vasodilating Activities

Grosso¹,

Boschi²,

Lazzarato³

et al. 2005

C&B

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Several NO donor 3,4-diphenylfuroxan (= 3,4-diphenyl-1,2,5-oxadiazole 2-oxide) derivatives were synthesized and tested for their COX-inhibiting activities. The products were found to be selective COX-2 inhibitors, similar to the structurally related furazans (3,4-diphenyl-1,2,5-oxadiazole), devoid of the NO release property. This behavior was confirmed by a molecular-docking study. The NO-dependent platelet anti-aggregatory and vasodilating activities of the new furoxans 5-7 were studied in vitro. These properties can be modulated by inserting an appropriate spacer between the 4-phenyl group and the furoxan ring, giving rise to new, selective COX-2 furoxan derivatives endowed with anti-aggregatory and vasodilating activities, and with potentially reduced cardiotoxicities.

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Water Soluble Furoxan Derivatives as NO Prodrugs

Abstract: log EC 50 ) 1.02 ((0.18)

Cited by 32 publications

References 0 publications

NO donors: Focus on furoxan derivatives

NO donors: Focus on furoxan derivatives

New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities

The Furoxan System: Design of Selective Nitric Oxide (NO) Donor Inhibitors of COX-2 Endowed with Anti-Aggregatory and Vasodilating Activities

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