Synthesis and biological evaluation of chalcone and stilbene based acetamidines as nitric oxide synthase inhibitors

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A Novel Prodrug of a nNOS Inhibitor with Improved Pharmacokinetic Potential

Under different pathological conditions, aberrant induction of neuronal nitric oxide synthase (nNOS) generates overproduction of NO that can cause irreversible cell damage. The aim of this study was to develop an amidoxime prodrug of a potent nNOS inhibitor, the benzhydryl acetamidine. We synthesized the benzhydryl acetamidoxime, which was evaluated in vitro to ascertain the potential NOS inhibitory activity, as well as conducting bioconversion into the parent acetamidine. The prodrug was also profiled for in vitro physicochemical properties, by determining the lipophilicity, passive permeation through the human gastrointestinal tract and across the blood-brain barrier by PAMPA, and chemical, enzymatic, and plasma stability. The obtained data demonstrate that the amidoxime prodrug shows an improved pharmacokinetic profile with respect to the acetamidine nNOS inhibitor, thus suggesting that it could be a promising lead compound to treat all those pathological conditions in which nNOS activity is dysregulated

The formulation of questions and the game to tackle a socio-scientific problem related to energy

Se relata una experiencia de enseñanza sobre energía, en la asignatura Introducción a la Física de 4to año de la Educación Secundaria, llevada a cabo durante el aislamiento social preventivo y obligatorio. Como estrategia docente se abordó un problema socio–científico, mediante preguntas con diferentes intenciones didácticas.La tercera fase de la secuencia didáctica consistió en plantear preguntas que promueven diferentes niveles de desarrollo cognitivo en los estudiantes.Además, para motivar a los estudiantes, se utilizó como recurso el juego virtual, para abordarlas preguntas y promover la integración y la transferencia de aprendizajes. Se presentan algunas consideraciones e implicancias en la enseñanzaAn experience of teaching about energy is related, in the course Introduction to Physics of the 4 th year of Secondary Education, carried out during preventive and compulsory social isolation. As a teaching strategy, a socio–scientific problemwas approached, through questions with different didactic intentions. The third phase of the didactic sequence consisted of asking questions thatpromote different levels of cognitive development in the students. In addition, to motivate the students, a virtual game was usedas a resource, to address the questions and promote the integration and transfer of learning. Some considerations andimplications in teaching are presented.Facultad de Humanidades y Ciencias de la Educació

Synthesis and Biological Evaluation of 2-Heteroarylthioalkanoic Acid Analogues of Clofibric Acid as Peroxisome Proliferator-Activated Receptor alpha Agonists

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Neuronal Nitric Oxide Synthase and Post-Translational Modifications in the Development of Central Nervous System Diseases: Implications and Regulation

In the Central Nervous System (CNS), Nitric Oxide (NO) is mainly biosynthesized by neuronal Nitric Oxide Synthase (nNOS). The dysregulated activation of nNOS in neurons is critical in the development of different conditions affecting the CNS. The excessive production of NO by nNOS is responsible for a number of proteins’ post-translational modifications (PTMs), which can lead to aberrant biochemical pathways, impairing CNS functions. In this review, we briefly revise the main implications of dysregulated nNOS in the progression of the most prevalent CNS neurodegenerative disorders, i.e., Alzheimer’s disease (AD) and Parkinson’s disease, as well as in the development of neuronal disorders. Moreover, a specific focus on compounds able to modulate nNOS activity as promising therapeutics to tackle different neuronal diseases is presented

Targeting neuronal nitric oxide synthase as a valuable strategy for the therapy of neurological disorders

The management of neurological disorders have huge and increasing human and economic costs. Despite this, there is a scarcity of effective therapeutics, and there is an extreme urgency for new and real treatments. In this short review we analyze some promising advancements in the search of new bioactive molecules targeting neuronal nitric oxide synthase (nNOS), an enzyme deputed to the biosynthesis of nitric oxide (NO). In different conditions of neuronal damages, this molecule is overproduced, contributing to the pathogenesis and progression of neuronal diseases. Two main approaches to modulate nNOS are discussed: a first one consisting in the direct inhibition of the enzyme by means of small organic molecules, which can be also active against other different targets involved in such diseases. A second section is dedicated to molecules able to prevent the formation of the ternary complex N-methyl-D-aspartate (NMDA)-type glutamate receptors, postsynaptic density-95 (PSD95) protein-nNOS, which is necessary to activate the latter for the biosynthesis of NO

Preface to Nitric Oxide Modulators in Health and Disease I

Nitric oxide (NO) is a small free radical molecule biosynthesized by nitric oxide synthases (NOS), a family of oxidoreductases responsible for the conversion of the natural substrate L-arginine into L-citrulline and NO [...

The formulation of questions and the game to tackle a socio-scientific problem related to energy

Se relata una experiencia de enseñanza sobre energía, en la asignatura Introducción a la Física de 4. o año de la Educación Secundaria, llevada a cabo durante el aislamiento social preventivo y obligatorio. Como estrategia docente se abordó un problema socio?científico, mediante preguntas con diferentes intenciones didácticas. La tercera fase de la secuencia didáctica consistió en plantear preguntas que promueven diferentes niveles de desarrollo cognitivo en los estudiantes. Además, para motivar a los estudiantes, se utilizó como recurso el juego virtual, para abordar las preguntas y promover la integración y la transferencia de aprendizajes. Se presentan algunas consideraciones e implicancias en la enseñanza.An experience of teaching about energy is related, in the course Introduction to Physics of the 4 th year of Secondary Education, carried out during preventive and compulsory social isolation. As a teaching strategy, a socio?scientific problem was approached, through questions with different didactic intentions. The third phase of the didactic sequence consisted of asking questions that promote different levels of cognitive development in the students. In addition, to motivate the students, a virtual game was used as a resource, to address the questions and promote the integration and transfer of learning. Some considerations and implications in teaching are presented.Fil: Maccallini, Yanina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.Fil: Wainmaier, Cristina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.Fil: Cabana, María Florencia. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina

The formulation of questions and the game to tackle a socio-scientific problem related to energy

Se relata una experiencia de enseñanza sobre energía, en la asignatura Introducción a la Física de 4to año de la Educación Secundaria, llevada a cabo durante el aislamiento social preventivo y obligatorio. Como estrategia docente se abordó un problema socio-científico, mediante preguntas con diferentes intenciones didácticas. La tercera fase de la secuencia didáctica consistió en plantear preguntas que promueven diferentes niveles de desarrollo cognitivo en los estudiantes. Además, para motivar a los estudiantes, se utilizó como recurso el juego virtual, para abordar las preguntas y promover la integración y la transferencia de aprendizajes. Se presentan algunas consideraciones e implicancias en la enseñanza.An experience of teaching about energy is related, in the course Introduction to Physics of the 4th year of Secondary Education, carried out during preventive and compulsory social isolation. As a teaching strategy, a socio-scientific problem was approached, through questions with different didactic intentions. The third phase of the didactic sequence consisted of asking questions that promote different levels of cognitive development in the students. In addition, to motivate the students, a virtual game was used as a resource, to address the questions and promote the integration and transfer of learning. Some considerations and implications in teaching are presented.Fil: Maccallini, Yanina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.Fil: Wainmaier, Cristina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina

The formulation of questions and the game to tackle a socio-scientific problem related to energy

Se relata una experiencia de enseñanza sobre energía, en la asignatura Introducción a la Física de 4to año de la Educación Secundaria, llevada a cabo durante el aislamiento social preventivo y obligatorio. Como estrategia docente se abordó un problema socio-científico, mediante preguntas con diferentes intenciones didácticas. La tercera fase de la secuencia didáctica consistió en plantear preguntas que promueven diferentes niveles de desarrollo cognitivo en los estudiantes. Además, para motivar a los estudiantes, se utilizó como recurso el juego virtual, para abordar las preguntas y promover la integración y la transferencia de aprendizajes. Se presentan algunas consideraciones e implicancias en la enseñanza.An experience of teaching about energy is related, in the course Introduction to Physics of the 4th year of Secondary Education, carried out during preventive and compulsory social isolation. As a teaching strategy, a socio-scientific problem was approached, through questions with different didactic intentions. The third phase of the didactic sequence consisted of asking questions that promote different levels of cognitive development in the students. In addition, to motivate the students, a virtual game was used as a resource, to address the questions and promote the integration and transfer of learning. Some considerations and implications in teaching are presented.Fil: Maccallini, Yanina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.Fil: Wainmaier, Cristina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina