A5022179453- Histone Deacetylase Inhibitors Research
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Receptor Mechanisms and Signaling
- HER2/EGFR in Cancer Research
- Alzheimer's disease research and treatments
- Quinazolinone synthesis and applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemistry and Chemical Engineering
- Synthesis and Catalytic Reactions
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Organic Chemistry Cycloaddition Reactions
- Metabolomics and Mass Spectrometry Studies
- Synthesis and biological activity
- Chemical Reaction Mechanisms
- Synthesis and Reactions of Organic Compounds
- Pharmacogenetics and Drug Metabolism
- Synthesis and Characterization of Heterocyclic Compounds
- Bioinformatics and Genomic Networks
- Medicinal Plants and Neuroprotection
Universidade Federal do Rio de Janeiro
2001-2025
Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular
2022-2025
National Institute of Science and Technology of Drugs and Medicines
2024-2025
University of Bologna
2020
Introduction The current drug discovery paradigm of 'one drug, multiple targets' has gained attention from both the academic medicinal chemistry community and pharmaceutical industry. This is in response to urgent need for effective agents treat multifactorial chronic diseases. molecular hybridization strategy a useful tool that been widely explored, particularly last two decades, design multi-target drugs.
Abstract Targeting histone deacetylases (HDACs) and phosphatidylinositol 3‐kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, molecular modeling of novel class N ‐acylhydrazone (NAH) derivatives that act as HDAC6/8 PI3Kα dual inhibitors. The surprising selectivity may be related to differences conformation active site. Cellular studies showed these compounds HDAC6 inhibition PI3/K/AKT/mTOR...
Background and Purpose Inhibitors of histone deacetylases (iHDACs) are promising drugs for neurodegenerative diseases. We have evaluated the therapeutic potential new iHDAC LASSBio‐1911 in Aβ oligomer (AβO) toxicity models astrocytes, key players neuroinflammation Alzheimer's disease (AD). Experimental Approach Astrocyte phenotype synapse density were by flow cytometry, Western blotting, immunofluorescence qPCR, vitro mice. Cognitive function was behavioural assays using a mouse model...
Rho-associated protein kinases (ROCK) play a pivotal role in various cellular processes and have emerged as therapeutic targets for neurodegenerative diseases such Alzheimer's disease (AD). Inhibition of ROCK affects the production key AD pathophysiological markers reduces neuroinflammation. This study aims to accelerate identification effective candidates neurodegeneration by drug repurposing. By conducting chemical space crystallographic structure analyses, we developed pharmacophoric map...
N-acylhydrazones (NAH) are privileged structures in chemistry and medicinal chemistry. The alkylation of NAH can profoundly alter the structural properties this subunit. In study, we describe conformational effects N- C-methylated derivatives, combining theoretical experimental data analysis. Methylation significantly affects structure through electronic influences changes lowest energy conformation. introduction methyl group induces a substantial steric impact, evident from alterations...
Histone deacetylases (HDACs) are key regulators of gene expression, influencing chromatin remodeling and playing a crucial role in various physiological pathological processes. Aberrant HDAC activity has been linked to cancer, neurodegenerative disorders, inflammatory diseases, making these enzymes attractive therapeutic targets. inhibitors (HDACis) have gained significant attention, particularly those containing zinc-binding groups (ZBGs), which interact directly with the catalytic zinc ion...
N-Acylhydrazones (NAH) are privileged structures in chemistry and medicinal chemistry. In this study, we describe the conformational effects of N- C-methylated N-acylhydrazone derivatives, combining theoretical experimental data analysis. Four derivatives (4-7) were synthesized structurally characterized to investigate impact methylation on their preferences electronic properties. The structural characterization by NMR spectroscopy, including 2D techniques (HSQC, HMBC, NOESY), confirmed...
Analisa, no contexto da Revolução de 1817, a atuação política e militar dos oficiais das ordenanças índios vilas do Rio Grande Norte criadas partir estabelecimento Diretório Índios (1757). A transformação pessoas indígenas em vassalos monarquia portuguesa originou mecanismos que permitiu sua participação na vida pública suas vilas, seja ocupando cargos nas câmaras, recebimento patentes militares, ou pela utilização mão obra precarizada. Entre os expoentes dessa atuação, destacou-se Hipólito...
Sigma-hole (σ-hole) bonds are interactions that gaining special attention in medicinal chemistry.
Thanks to the widespread use and safety profile of donepezil (1) in treatment Alzheimer's disease (AD), one most widely adopted multi-target-directed ligand (MTDL) design strategies is modify its molecular structure by linking a second fragment carrying an additional AD-relevant biological property. Herein, supported proposed combination therapy 1 quinone drug idebenone, we rationally designed novel 1-based MTDLs targeting Aβ oxidative pathways. By exploiting bioisosteric replacement...
Abstract PIK‐75 is a phosphoinositide‐3‐kinase (PI3K) α‐isoform‐selective inhibitor with high potency. Although published structure–activity relationship data show the importance of NO 2 and Br substituents in PIK‐75, none studies could correctly determine underlying reason for their importance. In this publication, we report first X‐ray crystal structure complex kinase GSK‐3β. The shows an unusual U‐shaped conformation within active site GSK‐3β that likely stabilized by atypical...
This work examines the current landscape of drug discovery and development, with a particular focus on chemical pharmacological spaces. It emphasizes importance understanding these spaces to anticipate future trends in discovery. The use cheminformatics data analysis enabled silico exploration spaces, allowing perspective drugs, approved drugs after 2020, clinical candidates, which were extracted from newly released ChEMBL34 (March 2024). enables identification areas be occupied, thereby...
MEDICINAL CHEMISTRY?.In Medicinal Chemistry, the knowledge, study and understanding of intermolecular interactions inherent to molecular recognition a ligand by its target bioreceptor are essential.This is because these interactions, which define complementarity between two, key analyze critically structure-activity relationship studies, allowing optimization modulation ligand.Thus, it necessary constant analysis related ligand-bioreceptor complexes.In general, all electrostatic in nature,...
Treatment of the Slipped Capital Femoral Epiphysis remains a cause concern due to fact that true knowledge etiopathogeny is unknown, as well one its major complications: chondrolysis. The conservative treatment controversial; it has been overlooked in studies and subjected intense criticism. purpose this study investigate results on hip patients displaying slipped capital femoral epiphysis, using plaster cast immobilization method link chondrolysis.The research was performed based following...
Pulmonary arterial hypertension (PAH) is a chronic cardiovascular disease that displays inflammatory components, which contributes to the difficulty of adequate treatment with available therapeutic arsenal. In this context, N-acylhydrazone derivative LASSBio-1359 was previously described as multitarget drug candidate able revert events associated progression PAH in animal models. However, spite having dual profile PDE4 inhibitor and adenosine A2A receptor agonist, does not present balanced...
Abstract Semiempirical methods can be applied to calculations of much larger systems than classical ab initio or DFT methods, reaching accuracy sometimes comparable with more advanced levels theory. These are important tools that used in research projects focused structure‐based drug design (SBDD). Thus, a notion the precision each method describing key‐interactions target receptors is necessary. With this goal mind, we several semiempirical (AM1, PM3, PM6, PM6‐D3, PM6‐D3H4, PM6‐DH2,...