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New heteroaryl nitrones with spin trap properties: Identification of a 4-furoxanyl derivative with excellent properties to be used in biological systems

Authordc.contributor.authorBarriga, Germán 
Authordc.contributor.authorOlea Azar, Claudio es_CL
Authordc.contributor.authorNorambuena, Ester es_CL
Authordc.contributor.authorCastro, Ana es_CL
Authordc.contributor.authorPorcal, Williams es_CL
Authordc.contributor.authorGerpe, Alejandra es_CL
Authordc.contributor.authorGonzález, Mercedes es_CL
Authordc.contributor.authorCerecetto, Hugo es_CL
Admission datedc.date.accessioned2010-07-13T15:47:13Z
Available datedc.date.available2010-07-13T15:47:13Z
Publication datedc.date.issued2010
Cita de ítemdc.identifier.citationBioorganic & Medicinal Chemistry 18 (2010) 795–802en_US
Identifierdc.identifier.otherdoi:10.1016/j.bmc.2009.11.053
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/121020
Abstractdc.description.abstractA new series of heteroaryl nitrones, 1–7, bearing furoxanyl and thiadiazolyl moieties, were evaluated for their free radical-trapping properties. The physicochemical characterization by electron paramagnetic resonance (EPR) demonstrated its capability to trap and stabilize oxygen-, carbon-, sulfur-, and nitrogen- centered free radicals. The 4-furoxanyl nitrone 3 (FxBN), a(Z)-(3-methylfuroxan-4-yl)-N-tert-butylnitrone, showed appropriate solubility in aqueous solution and taking into account that this physicochemical property is very important for biological applications, we studied it deeply in terms of its trapping and kinetic behaviors. For this, kinetic studies of the hydroxyl adduct decay gave rate constants kST of 1.22 1010 dm3 mol 1 s 1 and half-live up to 7200 s at physiological pH, without any artifactual signals. The ability of FxBN to directly traps and stabilizes superoxide free radical, with a half-life of 1620 s at physiological pH, was also demonstrated. Besides, FxBN-hydroxyl and -superoxide adducts exhibited distinct and characteristic EPR spectral patterns. Finally, we confirmed the ability of FxBN to act as spin trap in a specific biological system, that is, in the free radical production of experimental anti-trypanosomatid drugs using Trypanosoma cruzi microsomes as biological system. Moreover, previous observations of low FxBN toxicity transform it in a good candidate for in vivo spin trapping.en_US
Patrocinadordc.description.sponsorshipThe authors thank to Collaborative Project UdelaR (Uruguay)— CSIC (Spain) (#2006UY0009) and FONDECYT 1071068, 7040037, 7070282. W.P. thanks to PEDECIBA and CSIC (UdelaR) for fellowships.en_US
Lenguagedc.language.isoenen_US
Publisherdc.publisherELSEVIERen_US
Keywordsdc.subjectHeteroaryl nitronesen_US
Títulodc.titleNew heteroaryl nitrones with spin trap properties: Identification of a 4-furoxanyl derivative with excellent properties to be used in biological systemsen_US
Document typedc.typeArtículo de revistaen_US


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