01 December 2004
Indolalkylamines derivatives as antioxidant and neuroprotective agents in an experimental model of Parkinson’s diseaseElisenda Sanz, Manuel Romera, Lydia Belyk, J I Marco, Mercedes Unzeta
Med Sci Monit 2004; 10(12): BR477-484 :: ID: 13228
Background:The neuroprotective effect of N-(2-propynyl)2-(5-benzyloxy-indol)methylamine (PF 9601N), a novel MAO B inhibitor, and its metabolite FA 72 on the human neuroblastoma SHSY5Y cell line lesioned with (300 M) dopamine was assessed and compared with that of l-deprenyl assayed at identical experimental conditions.Material/Methods:Using this experimental model, PF 9601N showed a neuroprotective effect in a dose-dependent manner, and at a concentration of 10 μM a 20% recovery of cell viability was observed. However, the metabolite FA72 assayed under the same experimental conditions showed an increase in cell viability of nearly 50%. In the case of l-deprenyl, a concentration of 100 μM was necessary to recover only 10% of cell viability.Using this experimental model, PF 9601N showed a neuroprotective effect in a dose-dependent manner, and at a concentration of 10 μM a 20% recovery of cell viability was observed. However, the metabolite FA72 assayed under the same experimental conditions showed an increase in cell viability of nearly 50%. In the case of l-deprenyl, a concentration of 100 μM was necessary to recover only 10% of cell viability.Results:This neuroprotective effect could be explained in terms of the antioxidant capacity of PF 9601N. In this context, the antioxidant capacities of the novel series of MAO inhibitors, PF 9601N and its analogues, were evaluated by their inhibition of the auto-oxidation of dopamine to melanin and by the dichlorofluorescein and 2-deoxyribose methods.Conclusions:All of these compounds have the basic structure of an indole ring in common, but show different substituents at different positions in it. The corresponding structure-activity relationship studies allowed us to conclude that the presence of a benzyloxy group, or a hydroxy or methoxy group, at position 5 of the indol ring enhanced these antioxidant characteristics, presenting a decreasing order of antioxidant activity of the primary > secondary > tertiary amines. The antioxidant properties of PF 9601 N would explain its neuroprotective effect observed in SHSY5Y cells lesioned with dopamine.
Keywords: Antiparkinson Agents - chemistry, Antiparkinson Agents - pharmacology, Melanins - biosynthesis, Neuroprotective Agents - chemistry, Reactive Oxygen Species - analysis, Tryptamines - pharmacology, Animals, Antioxidants - therapeutic use, Antiparkinson Agents - therapeutic use, Brain - metabolism, Brain Chemistry, Cell Line, Tumor, Dopamine - pharmacology, Dose-Response Relationship, Drug, Indoles - therapeutic use, Melanins - biosynthesis, Monoamine Oxidase Inhibitors - therapeutic use, Neuroblastoma, Neuroprotective Agents - therapeutic use, Oxidative Stress - drug effects, Parkinson Disease - drug therapy, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species - metabolism, Selegiline - pharmacology, Tryptamines - pharmacology
This Week Editorial
20 September 2021 : EditorialEditorial: Autoantibodies to Components of the Immune System, Including Type 1 Interferons, and the Risk of Severe COVID-19
Med Sci Monit 2021; 27:e934766
22 September 2021 : EditorialEditorial: Global Regulatory Initiatives Deliver Accelerated Approval of the First Bispecific Therapeutic M...
Med Sci Monit In Press; DOI: 10.12659/MSM.934854
08 September 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit In Press; DOI: 10.12659/MSM.932788
16 July 2021 : Review articleSilent Hypoxemia in Patients with COVID-19 Pneumonia: A Review
Med Sci Monit In Press; DOI: 10.12659/MSM.930776
23 Sep 2021 : Animal ResearchForkhead Box Protein M1 Promotes Nasopharyngeal Carcinoma Cell Tumorigenesis Possibly via the Wnt/β-Catenin...
Med Sci Monit In Press; DOI: 10.12659/MSM.931970
22 Sep 2021 : EditorialEditorial: Global Regulatory Initiatives Deliver Accelerated Approval of the First Bispecific Therapeutic M...
Med Sci Monit In Press; DOI: 10.12659/MSM.934854
22 Sep 2021 : Clinical ResearchA Comparative Study of the Clinical Efficacy and Safety of Pneumatic Trabeculoplasty and Selective Laser Tr...
Med Sci Monit In Press; DOI: 10.12659/MSM.933454
20 Mar 2020 : Clinical ResearchSocial Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Diseas...
Med Sci Monit 2020; 26:e923921
15 Apr 2020 : Clinical ResearchPsychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...
Med Sci Monit 2020; 26:e924171
05 May 2020 : Review articleAn Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development
Med Sci Monit 2020; 26:e924700