GDP-mannose pyrophosphorylase is an efficient target in for citrus canker control.

Unlabelled: subsp. (Xcc) is a bacterium that causes citrus canker, an economically important disease that results in premature fruit drop and reduced yield of fresh fruit. In this study, we demonstrated the involvement of XanB, an enzyme with phosphomannose isomerase (PMI) and guanosine diphosphate-mannose pyrophosphorylase (GMP) activities, in Xcc pathogenicity.

Ligand-based virtual screening, molecular dynamics, and biological evaluation of repurposed drugs as inhibitors of proteasome.

Chagas disease is a well-known Neglected Tropical Disease, mostly endemic in continental Latin America, but that has spread to North America and Europe. Unfortunately, current treatments against such disease are ineffective and produce known and undesirable side effects. To find novel effective drug candidates to treat Chagas disease, we uniquely explore the proteasome as a recent biological target and, also, apply drug repurposing through different computational methodologies.

Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran.

Kefiran is a polysaccharide present in kefir grains that have been widely explored due to its potential health benefits. The objective of this work was to characterize and quantify the components present in the ethanolic extract of milk kefir grains; to study its pharmacokinetic and toxicological properties in silico and evaluate the acute toxicity of the kefiran in zebrafish. The prediction of pharmacokinetic properties was performed by QikProp software.

Synthesis, antitumor activity and in silico analyses of amino acid derivatives of artepillin C, drupanin and baccharin from green propolis.

Breast cancer has the highest incidence and mortality in females, while prostate cancer has the second-highest incidence in males. Studies have shown that compounds from Brazilian green propolis have antitumor activities and can selectively inhibit the AKR1C3 enzyme, overexpressed in hormone-dependent prostate and breast tumors. Thus, in an attempt to develop new cytotoxic inhibitors against these cancers, three prenylated compounds, artepillin C, drupanin and baccharin, were isolated from green propolis to synthesize new derivatives via coupling reactions with different amino acids.

Potential beneficial effects of kefir and its postbiotic, kefiran, on child food allergy.

Food allergies are known as the public health problem, affecting people of all age groups, but more commonly in babies and children, with consequences for nutritional status and quality of life. The increase in the consumption of healthy foods has consequently led to an increased demand for functional foods with specific health benefits. Thus, the pharmaceutical industry's interest in natural products has grown every time and is therefore considered as an alternative to synthetic drugs.

Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19.

The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (M), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure.

The Aspergillus fumigatus Phosphoproteome Reveals Roles of High-Osmolarity Glycerol Mitogen-Activated Protein Kinases in Promoting Cell Wall Damage and Caspofungin Tolerance.

The filamentous fungus can cause a distinct set of clinical disorders in humans. Invasive aspergillosis (IA) is the most common life-threatening fungal disease of immunocompromised humans. The mitogen-activated protein kinase (MAPK) signaling pathways are essential to the adaptation to the human host.

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review.

Among neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β-amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects.

New Horizons on Molecular Pharmacology Applied to Drug Discovery: When Resonance Overcomes Radioligand Binding.

One of the cornerstones of rational drug development is the measurement of molecular parameters derived from ligand-receptor interaction, which guides therapeutic windows definition. Over the last decades, radioligand binding has provided valuable contributions in this field as key method for such purposes. However, its limitations spurred the development of more exquisite techniques for determining such parameters.

3D descriptors calculation and conformational search to investigate potential bioactive conformations, with application in 3D-QSAR and virtual screening in drug design.

The knowledge of the bioactive conformation for an active hit is relevant because of the easier interpretation and the general quality of the recognition models of protein and ligand. With the aim of investigating potential bioactive conformations without previous structural knowledge of the molecular target, we present herewith a 'protocol' that could be used which includes generation of low-energy conformations, calculations of tridimensional descriptors and investigation of structural similarity via principal component analysis. The protocol was used in the search for potential bioactive conformations.

Toxicophoric and metabolic in silico evaluation of benzimidazole and phenylbenzamide derivatives with potential application as anticancer agents.

Poor pharmacokinetics and toxicity are responsible for most drug candidate failures. In order to attempt to some degree of ADMET (Absorption, Distribution, Metabolism, Excrection and Toxicity) information, in silico predictions arise currently as an interesting alternative to evaluate prototypes during early stages of the drug design processes, especially for anticancer candidates that constitute a class of therapeutic agents that exhibit substantial toxicity. A benzimidazole and a phenylbenzamide derivatives, previously identified as novel anticancer lead compounds able to prevent DNA binding to hnRNP K protein, were evaluated in silico regarding their metabolic profile and toxicity potential in order to give insights to the design of drug candidates with an adequate pharmaceutical profile.

In silico design and search for acetylcholinesterase inhibitors in Alzheimer's disease with a suitable pharmacokinetic profile and low toxicity.

Alzheimer's disease is a complex neurodegenerative disorder of the central nervous system, characterized by amyloid-β deposits, τ-protein aggregation, oxidative stress and reduced levels of acetylcholine in the brain. One pharmacological approach is to restore acetylcholine level by inhibiting acetylcholinesterase (AChE) with reversible inhibitors, such as galanthamine, thus helping to improve the cognitive symptoms of the disease. In order to design new galanthamine derivatives and search for novel, potential inhibitors with improved interactions, as well as a suitable pharmacokinetic profile and low toxicity, several molecular modeling techniques were applied.

Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy.

We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals.

Psoralen and bergapten: in silico metabolism and toxicophoric analysis of drugs used to treat vitiligo.

Purpose: To discuss the contribution of psoralen and bergapten metabolites on psoralens toxicity.

Methods: Computational chemistry prediction of metabolic reactions and toxicophoric groups based on the expert systems Derek and Meteor.

Results: a total of 15 metabolites were suggested for both psoralen and bergapten based on phase 1 and 2 biotransformations until the 3rd generation.

Molecular dynamics, density functional, ADMET predictions, virtual screening, and molecular interaction field studies for identification and evaluation of novel potential CDK2 inhibitors in cancer therapy.

In this work, we have used molecular dynamics, density functional theory, virtual screening, ADMET predictions, and molecular interaction field studies to design and propose eight novel potential inhibitors of CDK2. The eight molecules proposed showed interesting structural characteristics that are required for inhibiting the CDK2 activity and show potential as drug candidates for the treatment of cancer. The parameters related to the Rule of Five were calculated, and only one of the molecules violated more than one parameter.

Current topics in computer-aided drug design.

The addition of computer-aided drug design (CADD) technologies to the research and drug discovery approaches could lead to a reduction of up to 50% in the cost of drug design. Designing a drug is the process of finding or creating a molecule which has a specific activity on a biological organism. Development and drug discovery is a time-consuming, expensive, and interdisciplinary process whereas scientific advancements during the past two decades have altered the way pharmaceutical research produces new bioactive molecules.

Transdermal delivery of ketoprofen: the influence of drug-dioleylphosphatidylcholine interactions.

Purpose: Considering that most inflammatory diseases occur locally and near the body surface, transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) may be an interesting strategy for delivering these drugs directly to the diseased site. To optimize ketoprofen (KP) transdermal delivery we investigated the influence of dioleylphosphatidylcholine (DOPC) on skin permeation.

Materials And Methods: The formulations studied were: i) a physical mixture of KP and DOPC and ii) DOPC and KP complex, in a molar ratio of 1:3, obtained by dissolution of the components in chloroform followed by drying under a N2 atmosphere.

Three-dimensional structure of human adenine phosphoribosyltransferase and its relation to DHA-urolithiasis.

In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.

Fluorescence properties of tryptophan residues in the monomeric d-chain of Glossoscolex paulistus hemoglobin: an interpretation based on a comparative molecular model.

The primary structure of the 142 residue Glossoscolex paulistus d-chain hemoglobin has been determined from Edman degradation data of 11 endo-Glu-C peptides and 11 endo-Lys-C peptides, plus the results of Edman degradation of the intact globin. Tryptophan occupies positions 15, 33 and 129. Homology modeling allowed us to assign the positions of these Trp residues relative to the heme and its environment.