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Nervous System Diseases

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Nervous System Diseases	1

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Small molecule drug	1

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JNK3(c-Jun N-terminal kinase 3)	1

Author: Arraché Gonçalves, Guilherme ; Gonzalez, Laura Calle ; Silva, Éverton Edésio Dinis ; Moura, Sidnei ; Machado, Pablo ; Berger, Andresa ; Timmers, Luís Fernando Saraiva Macedo ; Muniz, Mauro Neves ; Basso, Luiz Augusto ; Perelló, Marcia Alberton ; Bizarro, Cristiano Valim ; Czeczot, Alexia de Matos

The crystallographic structure of the FolB enzyme from Mycobacterium tuberculosis (MtFolB), complexed with its inhibitor 8-mercaptoguanine (8-MG), was elucidated at a resolution of 1.95 Å. A novel series of S8-functionalized 8-MG derivatives were synthesised and evaluated as in vitro inhibitors of dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of MtFolB. These compounds exhibited IC₅₀ values in the submicromolar range. Evaluation of the activity for five compounds indicated their inhibition mode and inhibition constants. Molecular docking analyses were performed to determine the enzyme-inhibitor intermolecular interactions and ligand conformations upon complex formation. The inhibitory activities of all compounds against the M. tuberculosis H37Rv strain were evaluated. Compound 3e exhibited a minimum inhibitory concentration in the micromolar range. Finally, Compound 3e showed no apparent toxicity in both HepG2 and Vero cells. The findings presented herein will advance the quest for novel, specific inhibitors targeting MtFolB, an attractive molecular target for TB drug development.

01 Oct 2024·Epilepsy & Behavior

Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy

Article

Author: Cardozo Muller, Gabriel ; Amaro Alves Romariz, Simone ; de Almeida Xavier, Jaqueline ; Hermanus Schoorlemmer, Guus ; Vendramin Pasquetti, Mayara ; Klippel Zanona, Querusche ; Monteiro Longo, Beatriz ; Calcagnotto, Maria Elisa

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

01 Sep 2024·Clinical Neuropharmacology

Use of Citicoline in Attention-Deficit/Hyperactivity Disorder: A Pilot Study

Article

Author: Marchezan, Josemar ; Scheibe, Denise Bisolo ; Bücker, Joana ; Hübner, Isabel Barros

ObjectivesAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder in school-aged children. Although there are several drug treatment options, some patients do not have adequate therapeutic responses to conventional medications or experience considerable adverse effects. Citicoline is an endogenous molecule that has beneficial effects on attention, impulsivity, and memory and is a potential treatment for ADHD. This study aimed to evaluate the effect of citicoline in pediatric patients diagnosed with ADHD.MethodsThis randomized, crossover, double-blind, placebo-controlled clinical trial included with patients aged 7–12 years diagnosed with ADHD.ResultsAs a result, no statistically significant difference was noted between the use of citicoline and placebo in the evaluated parameters. The treatment had no adverse effects.ConclusionsCiticoline seems to be a safe molecule to be administered in the pediatric age group. Further studies are required to assess the therapeutic potential of citicoline in ADHD.

100 Deals associated with Universidade Do Vale Do Taquari

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100 Translational Medicine associated with Universidade Do Vale Do Taquari

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Pipeline

Pipeline Snapshot as of 26 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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