Furoxans as Nitric Oxide Donors. 4-Phenyl-3-furoxancarbonitrile: Thiol-Mediated Nitric Oxide Release and Biological Evaluation

Medana, Claudio; Ermondi, Giuseppe; Fruttero, Roberta; Stilo, Antonella Di; Ferretti, Carlo; Gasco, A.

doi:10.1021/jm00051a020

Cited by 114 publications

(81 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The attack of thiolate at the 3-position presumably produces similar transformations with the sole difference that one of the intermediates might generate nitrosothiols directly by interaction with thiols. The reaction of 4-phenyl-3-furoxancarbonitrile with an excess of thiophenol in a 7.4 pH buffer phosphate/ethanol mixture affords, among the final products, nitrite and 5-amino-3-phenyl-4-phenylthioisoxazole in comparable yields [11]. This suggests that, at least in this case, the attack of thiolate anion preferentially occurs at the 3-position.…”

Section: Furoxans As No Donorsmentioning

confidence: 83%

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

Section: Furoxans As No Donorsmentioning

confidence: 83%

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

show abstract

“…Thus the absence of nitrite/nitrate formation in phosphate-buffer cannot be concluded to indicate the absence of NO release from GEA 3175. A chemically related group of vasodilators, furoxans (1,2,5-oxadiazole-2-oxides) has been reported to release NO following chemical reactions with sulphydryl groups of low molecular weight thiols and proteins (Feelisch et al, 1992;Medana et al, 1994). Whether a similar mechanism accounts for the actions of GEA 3175 remains to be seen.…”

Section: Discussionmentioning

confidence: 99%

“…3-Morpholino-sydnonimine (SIN-1) an active metabolite of the anti-anginal drug molsidomine, has been shown to release NO together with superoxide anion (02-) (Feelisch, 1991;Hogg et al, 1992). Recently, some chemically different compounds have been reported to release NO directly or indirectly (Maragos et al, 1991;Feelisch et al, 1992;Mulsch et al, 1993;Medana et al, 1994;Kita et al, 1994;Salas et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide‐donating properties of mesoionic 3‐aryl substituted oxatriazole‐5‐imine derivatives

Kankaanranta

Rydell

Petersson

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

1 The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NOdonors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2 GEA 3162, GEA 3175, SIN-i and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 gM, respectively). All four compounds induced a dosedependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 gM) and inhibited 38-97% by oxyhaemoglobin (10-45 gM).3 All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-I and SNAP (100 pM) produced 50-70 gM NO2-+ NO3-as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4 The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-l and SNAP release nitric oxide.

show abstract

“…It is hypothesized that furoxan-ring opening to give a nitroso derivative is accomplished by thiolate attacking position 3 or 4. The derivative then releases NO − , which is oxidized to release NO [35][36][37]. The ester molecules characterized by a furoxan-based NO-releasing moiety have already been explored by several research groups for improving the pharmacological profile of the parent drugs [26,[38][39][40].…”

Section: Introductionmentioning

confidence: 99%

NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins

Han

et al. 2016

Molecules

View full text Add to dashboard Cite

A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10a-i) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC 50 of 0.81 µM and could also release 33.7 µmol/L NO at the time point of 60 min. Compounds 10a-i also showed cytotoxic selectivity between tumor and normal liver cells with IC 50 ranging from 22.1 to 33.9 µM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations.

show abstract

Furoxans as Nitric Oxide Donors. 4-Phenyl-3-furoxancarbonitrile: Thiol-Mediated Nitric Oxide Release and Biological Evaluation

Cited by 114 publications

References 5 publications

NO donors: Focus on furoxan derivatives

NO donors: Focus on furoxan derivatives

Nitric oxide‐donating properties of mesoionic 3‐aryl substituted oxatriazole‐5‐imine derivatives

NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins

Contact Info

Product

Resources

About