Development of eugenol derivatives with 5-LOX inhibitory activity.

Eugenol (4-allyl-2-methoxyphenol), is the major chemical constituent in the essential oil of numerous plant species. Several biological properties have been described for this molecule, including modulation of enzymatic targets relevant for the inflammatory response, such as 5-lipoxygenase (5-LOX). As so, there is interest in expanding the chemical space of this molecule to develop new molecules to be used in inflammatory conditions.

The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition.

Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation.

Dual action of benzaldehydes: Inhibiting quorum sensing and enhancing antibiotic efficacy for controlling Pseudomonas aeruginosa biofilms.

Quorum sensing (QS) has a central role in biofilm lifestyle and antimicrobial resistance, and disrupting these signaling pathways is a promising strategy to control bacterial pathogenicity and virulence. In this study, the efficacy of three structurally related benzaldehydes (4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde)) in disrupting the las and pqs systems of Pseudomonas aeruginosa was investigated using bioreporter strains and computational simulations. Additionally, these benzaldehydes were combined with tobramycin and ciprofloxacin antibiotics to evaluate their ability to increase antibiotic efficacy in preventing and eradicating P.

Montelukast and cefoperazone act as antiquorum sensing and antibiofilm agents against Pseudomonas aeruginosa.

Aims: Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control.

Methods And Results: The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of Ps.

Receptor-Based Virtual Screening of Large Libraries in a Multi-Level In Silico Approach.

Structure-based drug design (SBDD) has become an alternative to high throughput screening (HTS) as it reduces experimental costs and time. It works like a funnel, filtering out compounds that do not show good affinity (or score) toward a particular target, with known 3D structure.Here, we describe a protocol for structure-based drug design using a multi-level in silico approach, combining Molecular Docking, Virtual Screening, Molecular Dynamics Simulations and Free energy calculations to find new lead molecules for experimental testing, predict binding affinities and characterize binding modes.

Liposomal Formulations Loaded with a Eugenol Derivative for Application as Insecticides: Encapsulation Studies and In Silico Identification of Protein Targets.

A recently synthesized new eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate, with a high insecticidal activity against () insect cells, was encapsulated in the liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and 100% dioleoylphosphatidylglycerol (DOPG), aiming at the future application as insecticides. Compound-loaded DOPG liposomes have sizes of 274 ± 12 nm, while Egg-PC:Ch liposomes exhibit smaller hydrodynamic diameters (69.5 ± 7 nm), high encapsulation efficiency (88.

Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication.

New carvacrol and thymol derivatives as potential insecticides: synthesis, biological activity, computational studies and nanoencapsulation.

New compounds with potential insecticide activity were synthesized by structural modifications performed in the monoterpenoid phenolic moieties of carvacrol and thymol, resulting in a set of derivatives with the ether function containing the propyl, chloropropyl or hydroxypropyl chains, as well as a bicyclic ether with an unsaturated chain containing a carboxylic acid terminal. In addition, an analogue of carvacrol and thymol isomers bearing methoxyl, 1-hydroxyethyl and (3-chlorobenzoyl)oxy, instead of the three original methyl groups, was also synthesized. Several structural changes that resulted in diminished insecticide activity have been identified, but two significantly active molecules have been synthesized, one of them being less toxic to human cells than the naturally-derived starting materials.

Drug Repurposing Targeting MvfR Using Docking, Virtual Screening, Molecular Dynamics, and Free-Energy Calculations.

is an opportunistic Gram-negative bacterium responsible for acute and chronic infections in planktonic state or in biofilms. The sessile structures are known to confer physical stability, increase virulence, and work as a protective armor against antimicrobial compounds. can control the expression of genes, population density, and biofilm formation through a process called quorum sensing (QS), a rather complex and hierarchical system of communication.

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights.

A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY.

In Silico Identification of Possible Inhibitors for Protein Kinase B (PknB) of .

With tuberculosis still being one of leading causes of death in the world and the emergence of drug-resistant strains of (Mtb), researchers have been seeking to find further therapeutic strategies or more specific molecular targets. PknB is one of the 11 Ser/Thr protein kinases of Mtb and is responsible for phosphorylation-mediated signaling, mainly involved in cell wall synthesis, cell division and metabolism. With the amount of structural information available and the great interest in protein kinases, PknB has become an attractive target for drug development.

Selection of a new peptide homing SK-BR-3 breast cancer cells.

Breast cancer diagnosis remains a challenge, mostly due to its heterogeneity. This reality translates in delayed treatments, increasing treatment aggressiveness and lower chances of overall survival. The conventional detection techniques, although becoming increasingly sophisticated each year, still lack the ability to provide reliable conclusions without being time consuming, expensive, and uncomfortable for the patients.

The Biofilms Structural Database.

The Biofilms Structural Database (BSD) is a collection of structural, mutagenesis, kinetics, and inhibition data to understand the processes involved in biofilm formation. Presently, it includes curated information on 425 structures of proteins and enzymes involved in biofilm formation and development for 42 different bacteria. It is available at www.

A Flow Cytometric and Computational Approaches to Carbapenems Affinity to the Different Types of Carbapenemases.

The synergy of carbapenem combinations regarding Enterobacteriaceae producing different types of carbapenemases was study through different approaches: flow cytometry and computational analysis. Ten well characterized Enterobacteriaceae (KPC, verona integron-encoded metallo-β-lactamases -VIM and OXA-48-like enzymes) were selected for the study. The cells were incubated with a combination of ertapenem with imipenem, meropenem, or doripenem and killing kinetic curves performed with and without reinforcements of the drugs.