Liquid crystal nanoparticles for oral combination antibiotic therapies: A strategy towards protecting commensal gut bacteria during treatment.

Antibiotics are essential for treating infections and reducing risks during medical interventions. However, many commonly used antibiotics lack the physiochemical properties for an efficient oral administration when treating systemic infection. Instead, we are reliant on intravenous delivery, which presents complications outside of clinical settings.

Preparation of Simple Bicyclic Carboxylate-Rich Alicyclic Molecules for the Investigation of Dissolved Organic Matter.

Dissolved organic matter (DOM) is a vast and complex chemical mixture that plays a key role in the mediation of the global carbon cycle. Fundamental understanding of the source and fate of oceanic organic matter is obscured due to poor definition of the key molecular contributors to DOM, which limits accurate sample analysis and prediction of the Earth's carbon cycle. Previous work has attempted to define the components of the DOM through a variety of chromatographic and spectral techniques.

Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry.

The unwanted accumulation of marine micro- and macroorganisms such as algae and barnacles on submerged man-made structures and vessel hulls is a major challenge for any marine operation. Known as biofouling, this problem leads to reduced hydrodynamic efficiency, significantly increased fuel usage, microbially induced corrosion, and, if not managed appropriately, eventual loss of both performance and structural integrity. Ship hull biofouling in the international maritime transport network conservatively accounts for 0.

Antimicrobial Peptides Incorporating Halogenated Marine-Derived Amino Acid Substituents.

Small synthetic mimics of cationic antimicrobial peptides represent a promising class of compounds with leads in clinical development for the treatment of persistent microbial infections. The activity and selectivity of these compounds rely on a balance between hydrophobic and cationic components, and here, we explore the activity of 19 linear cationic tripeptides against five different pathogenic bacteria and fungi, including clinical isolates. The compounds incorporated modified hydrophobic amino acids inspired by motifs often found in bioactive marine secondary metabolites in combination with different cationic residues to probe the possibility of generating active compounds with improved safety profiles.

Characterization of a Newly Available Coastal Marine Dissolved Organic Matter Reference Material (TRM-0522).

Recent methodological advances have greatly increased our ability to characterize aquatic dissolved organic matter (DOM) using high-resolution instrumentation, including nuclear magnetic resonance (NMR) and mass spectrometry (HRMS). Reliable DOM reference materials are required for further method development and data set alignment but do not currently exist for the marine environment. This presents a major limitation for marine biogeochemistry and related fields, including natural product discovery.

Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses.

Drugs targeting SARS-CoV-2 could have saved millions of lives during the COVID-19 pandemic, and it is now crucial to develop inhibitors of coronavirus replication in preparation for future outbreaks. We explored two virtual screening strategies to find inhibitors of the SARS-CoV-2 main protease in ultralarge chemical libraries. First, structure-based docking was used to screen a diverse library of 235 million virtual compounds against the active site.

Spatial Distribution and Stability of Cholinesterase Inhibitory Protoberberine Alkaloids from .

During a research program to identify new cholinesterase inhibitors of natural origin, two new 7,8-didehydroprotoberberine alkaloids ( and ) and nine known compounds (-) were isolated from the capsules of the common ornamental poppy, (previously ). Despite their reported instability, the 7,8-didehydroprotoberberines isolated herein appeared relatively stable, particularly as their trifluoroacetic acid salts. The spatial distributions of the isolated alkaloids were also analyzed using desorption electrospray ionization imaging mass spectrometry.

A Genetically Encoded Picolyl Azide for Improved Live Cell Copper Click Labeling.

Bioorthogonal chemistry allows rapid and highly selective reactivity in biological environments. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a classic bioorthogonal reaction routinely used to modify azides or alkynes that have been introduced into biomolecules. Amber suppression is an efficient method for incorporating such chemical handles into proteins on the ribosome, in which noncanonical amino acids (ncAAs) are site specifically introduced into the polypeptide in response to an amber (UAG) stop codon.

Phidianidine A and Synthetic Analogues as Naturally Inspired Marine Antifoulants.

Stationary and slow-moving marine organisms regularly employ a natural product chemical defense to prevent being colonized by marine micro- and macroorganisms. While these natural antifoulants can be structurally diverse, they often display highly conserved chemistries and physicochemical properties, suggesting a natural marine antifouling pharmacophore. In our current report, we investigate the marine natural product phidianidine A, which displays several chemical properties found in highly potent marine antifoulants.

Sulfadiazine Masquerading as a Natural Product from (Scilloideae).

The structure of 2,4-(4'-aminobenzenamine)pyrimidine (), a pyrimidine alkaloid previously isolated from the bulbs of (Asparagaceae, synonym ), has been revised. These conclusions were met via comparison of reported NMR and EIMS data with those obtained from synthetic standards. The corrected structure is the antibiotic sulfadiazine (), which has likely been isolated as a contaminant from the site of collection.

Cellular uptake of self-assembled phytantriol-based hexosomes is independent of major endocytic machineries.

Despite increasing interests in non-lamellar liquid crystalline dispersions, such as hexosomes, for drug delivery, little is known about their interactions with cells and mechanism of cell entry. Here we examine the cellular uptake of hexosomes based on phytantriol and mannide monooleate by HeLa cells using live cell microscopy in comparison to conventional liposomes. To investigate the importance of specific endocytosis pathways upon particle internalization, we silenced regulatory proteins of major endocytosis pathways using short interfering RNA.

Natural cholinesterase inhibitors from marine organisms.

Covering: Published between 1974 up to 2018Inhibition of cholinesterases is a common approach for the management of several disease states. Most notably, cholinesterase inhibitors are used to alleviate the symptoms of neurological disorders like dementia and Alzheimer's disease and treat myasthenia gravis and glaucoma. Historically, most drugs of natural origin have been isolated from terrestrial sources and inhibitors of cholinesterases are no exception.

Photoactivated Colibactin Probes Induce Cellular DNA Damage.

Colibactin is a small molecule produced by certain bacterial species of the human microbiota that harbour the pks genomic island. Pks bacteria induce a genotoxic phenotype in eukaryotic cells and have been linked with colorectal cancer progression. Colibactin is produced in a benign, prodrug form which, prior to export, is enzymatically matured by the producing bacteria to its active form.

Synthesis and Spectroscopic Properties of Fluorinated Coumarin Lysine Derivatives.

The site-selective incorporation of fluorescent amino acids into proteins has emerged as a valuable alternative to expressible protein reporters. For successful application, a robust and scalable, yet flexible, route to non-natural amino acids is required. This work describes an improved synthesis of coumarin-conjugated lysine derivatives where fluorinated variants are accessed.

Design and Biological Evaluation of Antifouling Dihydrostilbene Oxime Hybrids.

By combining the recently reported repelling natural dihydrostilbene scaffold with an oxime moiety found in many marine antifoulants, a library of nine antifouling hybrid compounds was developed and biologically evaluated. The prepared compounds were shown to display a low antifouling effect against marine bacteria but a high potency against the attachment and growth of microalgae down to MIC values of 0.01 μg/mL for the most potent hybrid.

Prevention of Marine Biofouling Using the Natural Allelopathic Compound Batatasin-III and Synthetic Analogues.

The current study reports the first comprehensive evaluation of a class of allelopathic terrestrial natural products as antifoulants in a marine setting. To investigate the antifouling potential of the natural dihydrostilbene scaffold, a library of 22 synthetic dihydrostilbenes with varying substitution patterns, many of which occur naturally in terrestrial plants, were prepared and assessed for their antifouling capacity. The compounds were evaluated in an extensive screen against 16 fouling marine organisms.

Palladium-Mediated Approach to Coumarin-Functionalized Amino Acids.

Incorporation of the fluorogenic l-(7-hydroxycoumarin-4-yl)ethylglycine into proteins is a valuable biological tool. Coumarins are typically accessed via the Pechmann reaction, which requires acidic conditions and lacks substrate flexibility. A Pd-mediated coupling is described between o-methoxyboronic acids and a glutamic acid derived (Z)-vinyl triflate, forming latent coumarins.

Probing the Structure-Activity Relationship of the Natural Antifouling Agent Polygodial against both Micro- and Macrofoulers by Semisynthetic Modification.

The current study represents the first comprehensive investigation into the general antifouling activities of the natural drimane sesquiterpene polygodial. Previous studies have highlighted a high antifouling effect toward macrofoulers, such as ascidians, tubeworms, and mussels, but no reports about the general antifouling effect of polygodial have been communicated before. To probe the structural and chemical basis for antifouling activity, a library of 11 polygodial analogues was prepared by semisynthesis.

Synthetic analogs of stryphnusin isolated from the marine sponge Stryphnus fortis inhibit acetylcholinesterase with no effect on muscle function or neuromuscular transmission.

The marine secondary metabolite stryphnusin (1) was isolated from the boreal sponge Stryphnus fortis, collected off the Norwegian coast. Given its resemblance to other natural acetylcholinesterase antagonists, it was evaluated against electric eel acetylcholinesterase and displayed inhibitory activity. A library of twelve synthetic phenethylamine analogs, 2a-7a and 2b-7b, containing tertiary and quaternary amines respectively were synthesized to investigate the individual structural contributions to the activity.

Marine AChE inhibitors isolated from Geodia barretti: natural compounds and their synthetic analogs.

Barettin, 8,9-dihydrobarettin, bromoconicamin and a novel brominated marine indole were isolated from the boreal sponge Geodia barretti collected off the Norwegian coast. The compounds were evaluated as inhibitors of electric eel acetylcholinesterase. Barettin and 8,9-dihydrobarettin displayed significant inhibition of the enzyme, with inhibition constants (Ki) of 29 and 19 μM respectively towards acetylcholinesterase via a reversible noncompetitive mechanism.