Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11956
Title: Nitrone-based therapeutics for neurodegenerative diseases: Their use alone or in combination with lanthionines
Authors: Floyd, Robert A.
Faria Neto, Hugo C. Castro
Zimmerman, Guy A.
Hensley, Kenneth
Towner, Rheal A.
Affilliation: Oklahoma Medical Research Foundation. Experimental Therapeutics. Oklahoma City, OK, USA,
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Immunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Immunofarmacologia. Rio de Janeiro, RJ, Brasil / University of Utah School of Medicine. Department of Medicine. Salt Lake City, Utah, USA.
University of Toledo Medical Center. Department of Pathology and Department of Neurosciences. Toledo, OH.
Oklahoma Medical Research Foundation. Advanced Magnetic Resonance Center. Oklahoma City, OK, USA.
Abstract: The possibility of free radical reactions occurring in biological processes led to the development and employment of novel methods and techniques focused on determining their existence and importance in normal and pathological conditions. For this reason the use of nitrones for spin trapping free radicals became widespread in the 1970s and 1980s, when surprisingly the first evidence of their potent biological properties was noted. Since then widespread exploration and demonstration of the potent biological properties of phenyl-tert-butylnitrone (PBN) and its derivatives took place in preclinical models of septic shock and then in experimental stroke. The most extensive commercial effort made to capitalize on the potent properties of the PBN-nitrones was for acute ischemic stroke. This occurred during 1993–2006, when the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective. As summarized in this review, because of its excellent human safety profile, 2,4-disulfonylphenyl PBN, now called OKN-007 in the cancer studies, was tested as an anti-cancer agent in several preclinical glioma models and shown to be very effective. Based on these studies this compound is now scheduled to enter into early clinical trials for astrocytoma/glioblastoma multiforme this year. The potential use of OKN-007 in combination with neurotropic compounds such as the lanthionine ketamine esters is discussed for glioblastoma multiforme as well as for various other indications leading to dementia, such as aging, septic shock, and malaria infections. There is much more research and development activity ongoing for various indications with the nitrones, alone or in combination with other active compounds, as briefly noted in this review.
Keywords: Nitrones
Glioma
Glioblastoma multiforme
Cancer
Dementia
Septic shock
Malaria dementia
Aging
Lanthionine
PBN
NXY-059
OKN-007
Spin trapping
Free radicals
DeCS: Glioma
Glioblastoma
Câncer
Demência
Malaria
Envelhecimento
Detecção de Spin
Radicais Livres
Issue Date: 2013
Publisher: Elsevier
Citation: FLOYD, Robert A.; et al. Nitrone-based therapeutics for neurodegenerative diseases: Their use alone or in combination with lanthionines. Free Radical Biology and Medicine, v.62, p.145-156, Sept. 2013.
ISSN: 0891-5849
10.1016/j.freeradbiomed.2013.01.033
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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