Human sirtuin 2 inhibitors, their mechanisms and binding modes.

The silent information regulator (sirtuin) is a family of enzymes involved in epigenetic processes with lysine deacetylase activity, having as substrates histones and other proteins. They participate in a wide range of cellular and pathologic processes, such as gene expression, cell division and motility, oxidative-induced stress management, metabolic control and carcinogenesis, among others, thus presenting as interesting therapeutic targets. In this article, the authors describe the inhibitory mechanisms and binding modes of the human sirtuin 2 (hSIRT2) inhibitors, which had their complexes with the enzyme structurally characterized.

Machine learning methods applied for the prediction of biological activities of triple reuptake inhibitors.

Major depressive disorder (MDD) is characterized by a series of disabling symptoms like anhedonia, depressed mood, lack of motivation for daily tasks and self-extermination thoughts. The monoamine deficiency hypothesis states that depression is mainly caused by a deficiency of monoamine at the synaptic cleft. Thus, major efforts have been made to develop drugs that inhibit serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transporters and increase the availability of these monoamines.

Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways.

Rheumatoid arthritis (RA) development is strongly associated with cigarette smoke exposure, which activates the aryl hydrocarbon receptor (AhR) as a trigger for Th17 inflammatory pathways. We previously demonstrated that the exposure to hydroquinone (HQ), one of the major compounds of cigarette tar, aggravates the arthritis symptomatology in rats. However, the mechanisms related to the HQ-related RA still remain elusive.

Parasitic sirtuin 2 as an opportunity in drug discovery.

Infections caused by protozoans remain a public health issue, especially in tropical countries. Serious adverse events, lack of efficacy at the different stages of the infection and routes of administration that have a negative impact on treatment adherence are some of the problems with currently available therapy against these diseases. Here we describe an epigenetic target, sirtuin 2 and its related proteins, that is promising given the results in phenotypic assays and models against Sir2 of , , , , and parasites.

Antibodies Against the Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants.

Malaria is a human parasitic disease distributed in many tropical countries and caused by various species. has the largest geographical distribution of the species and is predominant in the Americas, including Brazil. Only a small number of vaccine formulations have successfully reached clinical trials relative to their counterparts.

Insights into Newly Approved Drugs from a Medicinal Chemistry Perspective.

The development of new drugs is becoming notably harder each decade. To overcome the present pitfalls in the drug development pipeline, such as those related to potency, selectivity, or absorption, distribution, metabolism, excretion and toxicity properties, medicinal chemistry strategies need to be in continuous evolution and need to become even more multidisciplinary. In this review, we present how structure-based, ligand-based, and fragment-based drug design (SBDD, LBDD, and FBDD, respectively) and their respective techniques were used for the design and optimization of successful cases of New Molecular Entities (NMEs) approved by the Food and Drug Administration (FDA).

Antiplasmodial activity of sulfonylhydrazones: and approaches.

Malaria is still a life-threatening public health issue, and the upsurge of resistant strains requires continuous generation of active molecules. In this work, 35 sulfonylhydrazone derivatives were synthesized and evaluated against chloroquine-sensitive (3D7) and resistant (W2) strains. The most promising compound, 5b, had an IC of 0.

Ligand and structure-based virtual screening applied to the SARS-CoV-2 main protease: an repurposing study.

The identification of drugs for the coronavirus disease-19 pandemic remains urgent. In this manner, drug repurposing is a suitable strategy, saving resources and time normally spent during regular drug discovery frameworks. Essential for viral replication, the main protease has been explored as a promising target for the drug discovery process.

Fragment-based drug discovery as alternative strategy to the drug development for neglected diseases.

Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery emerged as one of the most promising alternatives to the traditional methods of drug development.