In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor.

O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. We developed a classification model using docking scores and ligand descriptors. The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor.

Farmacologia de drogas vasoativas / Pharmacology of vasoactive drugs

As doenças vasculares periféricas (DVPS) caracterizam-se como um problema de circulação nas veias, artérias e sistema linfático. O tratamento primordial para as DVPS é a mudança de hábitos de vida, alimentação e prática de atividade física. A terapia farmacológica inclui a utilização de drogas vasoativas, as quais são utilizadas nas arteriopatias e nas doenças veno-linfáticas. O objetivo deste estudo foi pesquisar em literatura científica sobre a utilização e farmacologia das drogas vasoativas, enfatizando a eficácia da administração e ação local dessas drogas.

Peripheral vascular diseases (PVDS) are characterized as a circulation problem in the veins, arteries, and lymphatic system. The main therapy consists of changes in lifestyle such as diet and physical activity. The pharmacological therapy includes the use of vasoactive drugs, which are used in arteriopathies and venolymphatic disorders. The goal of this study was to research the scientific literature on the use and pharmacology of vasoactive drugs, emphasizing the efficacy of their local actions and administration.

Efeitos secundários potencialmente desejáveis dos anestésicos locais: [revisão] / Potentially desirable secondary effects of local anesthetics: [review]

Apesar do uso dos anestésicos locais (ALs) ter a finalidade principal de produzir bloqueios nervosos pela inibição dos canais de Na+, a literatura tem mostrado que esses agentes podem ter ações farmacológicas adicionais, afetando também, os canais de potássio e de cálcio e agindo em mecanismos intracelulares. Os ALs podem, além de causar anestesia, agir diretamente sobre outros receptores e suas vias de sinalização que estão envolvidos nos processos de inflamação, ativação plaquetária, nocicepção, dor periférica e arritmias, dentre outras, buscando cada vez mais, uma melhor eficácia e segurança clínica, além de novas e potencialmente úteis propriedades para os ALs. Assim, o objetivo deste estudo foi pesquisar em literatura científica e descrever uma revisão da farmacologia e dos efeitos adicionais potencialmente desejáveis dos principais anestésicos locais usados na clínica médica.

Despite the use of local anesthetics (LAs) having the primary purpose of producing nerve blockages by the inhibition of Na+ channels, the literature has shown that these agents may have additional pharmacological actions, also affecting the potassium and calcium channels and acting on intracellular mechanisms. Besides causing anesthesia, the LAs may act directly on other receptors and their signaling pathways which are involved in processes of inflammation, platelet activation, nociception, peripheral pain and arrhythmias, among others, increasingly seeking better clinical efficacy and safety, in addition to new and potentially useful properties for the LAs. Therefore, the aim of this study is to search the scientific literature and review the pharmacology and the additional potentially desirable effects of the LAs used in medical clinic.

Antiinflamatórios não-esteroidais e sua farmacologia local: [revisão] / Non-steroidal anti-inflammatory drugs and their local pharmacology: [review]

Os antiinflamatórios não-esteroidais (AINES) são geralmente usados para reduzir a dor e inflamação resultantes de diversos tipos de lesões. Apesar de normalmente serem administrados por via oral, seu uso local tem atraído a atenção de profissionais da área médica e de pesquisadores interessados em comprovar a disponibilidade aumentada desses medicamentos em locais próximos a área lesionada. A presente revisão enfatiza a terapia local, principalmente a via intradérmica, como uma alternativa altamente promissora para a administração de AINES.

Non-steroidal anti-inflammatory drugs (NSAIDS) are often used to reduce pain and inflammation from various types of injuries. Although these drugs are usually orally taken, localized administration has attracted the attention of medical professionals and researchers interested in proving the enhanced availability of these medicines close to the injuries. This review briefly analyzes the localized therapy, especially the intradermal one, as a promising alternative to the administration of NSAIDS.