NO donors: Focus on furoxan derivatives

Abstract

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.

Synthesis and SAR Studies of New Oxadiazole-2-oxide Derivatives with Remarkable In Vitro Activity against Schistosoma japonicum

“…This structure activity relationship (SAR) could have important implications for further drug development of the oxadiazole-2-oxides against schistosomiasis. The oxadiazole-2-oxide core is a class of NO donating compounds [22]. These compounds show us that schistosomiasis may have other targets, while different compounds work on different target group.…”

Synthesis, structural characterization and cytotoxic activity of heterocyclic compounds containing the furoxan ring

“…The reaction mixture was stirred for 72 h at room temperature until disappearance of the initial compound 12b (TLC monitoring). Then water (15 mL) was added, the resulting mixture was extracted with CHCl 3 (3x20 mL), washed with water and dried over MgSO 4 5-(4-oxo-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-ylthio)methyl-1-(5-oxido-3-phenyl-1,2,5-oxadiazol-5-ium-4-yl)-1H-1,2,3-triazole-4-carboxylate (5d -1-yl)methyl-1-(5-oxido-3-phenyl-1,2,5-oxadiazol-5-ium-4-yl)-1H-1,2,3-triazole-4 -3-phenyl-1,2,5-oxadiazol-5-ium-4-yl)-5-(pyrrolidin-1-yl)methyl-1H-1,2,3-triazole-4 5-(cycloalkylamino)methyl-1-(5-oxido-3-phenyl-1,2,5-oxadiazol-5-ium-4-yl)-1H-1,2,3-triazole-4-carbonyl azide 17a,b. To a solution of the corresponding hydrazide 16 (5 mmol) in AcOH-dioxane (30 mL, 1:1 ν/ν) mixture at 2-6 o C the solution of NaNO 2 (1.04 g, 15 mmol) in water (1.5 mL) was added for 15 min.…”

“…A solution of NaHCO 3 (640 mg, 7.6 mmol) in water (30 mL) was added to the ester 12a (720 mg, 1.9 mmol). The resulting mixture was refluxed for 2 h, then cooled to room temperature, treated with dilute hydrochloric acid, extracted with EtOAc (3x20 mL) and dried over MgSO 4 3-phenyl-4-(5-R-1H-1,2,3-triazol-1-yl)-1,2,5-oxadiazole 2-oxides 5k,n The corresponding carboxylic acid 5g or 18 (2 mmol) was dissolved in acetic acid (20 mL), the resulting solution was refluxed for 30 min for compound 5g or for 3 h for compound 18. Then AcOH was evaporated under reduced pressure.…”

“…Over thirty years ago it was established that NO is one of the crucial regulator molecules for cellular metabolism, affecting various physiological and pathophysiological processes. [4][5][6] Many different types of compounds have been synthesized and tested as NO donors (guanidines, nitramines, oximes, mesoionic systems, heterocyclic N-oxides, etc. ), [7][8][9] including the 1,2,5-oxadiazole 2-oxides (furoxans) which are capable of exogenous NO release at the presence of thiol cofactors.…”

Multitarget drugs: Focus on the NO-donor hybrid drugs

“…Since the capacity to release NO by the furoxan system can be modulated by changing the substituents at the ring and, in general, it is in-A. GASCO et al creased by the presence of electron-withdrawing groups, furoxan moieties appear to be flexible tools for balancing the designed hybrids [11,15].…”