Bioactive Molecules Research Articles

Synthesis of Dienamides via Palladium-catalyzed Oxidative N-α,β-Dehydrogenation of Amides.

Enamides and their derivatives are prominent bioactive pharmacophores found in various bioactive molecules. Herein we report a palladium-catalyzed oxidative N-α,β-dehydrogenation of amides to produce a range of enamides with high yields and excellent tolerance toward different functional groups. Mechanistic studies indicate that the reaction involves allylic C(sp3)-H activation followed by β-H elimination. The effectiveness of this approach is demonstrated through late-stage functionalization of bioactive molecules and the synthesis of valuable compounds through product elaboration.

Valorizing the potential of saffron petals extract for aluminium corrosion control: An integrated approach involving extraction, experimental and computational analysis

Our study focuses on enhancing the antioxidant potential of saffron petals extract (SPE) as a sustainable corrosion inhibitor for aluminium (Al) in a 3.5% NaCl solution. The phytochemical screening and antioxidant activity are identified. Various investigative methodologies, including experimental techniques such as Electrochemical Impedance Spectroscopy (EIS) and Potentiodynamic Polarization (PDP), were employed to evaluate the effectiveness of this compound in inhibiting corrosion. Computational analysis, involving Density Functional Theory (DFT) and Molecular Dynamics (MD) simulations, were utilized to carry out a Theoretical study on the main constituents of SPE. The surface characteristics and composition of the corroded Al were examined using a combination of Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectroscopy (EDX) and Fourier Transform Infrared Spectroscopy (FT-IR). The Electrochemical results suggest that the effectiveness of the inhibitor was dependent on its concentration, reaching 95.11% at 500 ppm of SPE. The PDP indicates that mixed inhibition control effectively slowed down the corrosion of Al. Furthermore, the adsorption behaviour of SPE onto Al follows to the Langmuir isotherm model. SEM, EDX and FT-IR analyses further verified significant alterations in the surface morphology and roughness of Al and confirming the successful formation of a protective layer on the Al surface. Ultraviolet-Visible spectroscopy (UV-Vis) reveals evidence of interaction between Al and the SPE molecules. Computational studies substantiated these observations, demonstrating the reactivity and adsorption patterns of the evaluated major bioactive molecules of SPE on the Al surface.

Iridium‐Catalysed C(sp3)−H Activation and Hydrogen Isotope Exchange via Nitrogen‐Based Carbonyl Directing Groups

AbstractGrowing interest in improved structural diversity within the pharmaceutical industry has led to a focus on more sp3‐rich drug frameworks. Meanwhile, spiralling pharmaceutical research and development costs continue to require expedited adsorption, distribution, metabolism, excretion, and toxicity studies, which are heavily reliant on the use of molecules incorporating deuterium and tritium. Herein, we report an iridium catalyzed C(sp3)−H activation and hydrogen isotope exchange (HIE) methodology capable of utilizing pharmaceutically ubiquitous nitrogen‐based carbonyl directing groups. High levels of deuterium incorporation (>80% in 37 of the examples) are demonstrated across a range of substrates (5‐, 6‐, and 7‐membered lactams, cyclic carbamates and ureas, acyclic amides), with tolerance of a range of common functional groups (aryl, alkoxy, halogen, ester, alcohol, sulfonamide) and predictable regioselectivity. The applicability of this methodology was demonstrated with up to 98% deuterium incorporation observed in a range of challenging bioactive molecules such as Nefiracetam, Praziquantel, and Unifiram. Density functional theory has provided mechanistic insight into the C−H activation and HIE at both the expected site of incorporation and an unexpected aryl labelling via a 7‐membered metallocyclic intermediate.

The 18F‐Difluoromethyl Group: Challenges, Impact and Outlook

AbstractThe difluoromethyl functionality has proven useful in drug discovery, as it can modulate the properties of bioactive molecules. For PET imaging, this structural motif has been largely underexploited in (pre)clinical radiotracers due to a lack of user‐friendly radiosynthetic routes. This Minireview provides an overview of the challenges facing radiochemists and summarises the efforts made to date to access 18F‐difluoromethyl‐containing radiotracers. Two distinct approaches have prevailed, the first of which relies on 18F‐fluorination. A second approach consists of a 18F‐difluoromethylation process, which uses 18F‐labelled reagents capable of releasing key reactive intermediates such as the [18F]CF2H radical or [18F]difluorocarbene. Finally, we provide an outlook for future directions in the radiosynthesis of [18F]CF2H compounds and their application in tracer radiosynthesis.

Nonclassical Zwitterions as a Design Principle to Reduce Lipophilicity without Impacting Permeability.

The ionization of bioactive molecules impacts many ADME-relevant physicochemical properties, in particular, solubility, lipophilicity, and permeability. Ampholytes contain both acidic and basic groups and are distinguished as ordinary ampholytes and zwitterions. An influential review states that zwitterions only exist if the acidic pKa is significantly lower than the basic pKa. Through concordance of measured and calculated pKa and log P, we show that the zwitterionic behavior of several marketed drugs and natural products occurs despite a low or negative ΔpKa. These nonclassical zwitterions are characterized by a weak acidic and basic pKa and conjugation through an extended aromatic system, often including pseudorings via intramolecular hydrogen bonds. In contrast to most classical zwitterions, nonclassical zwitterions can exhibit excellent permeability. As permeability and lipophilicity are typically correlated, the combination of low lipophilicity and high permeability makes nonclassical zwitterions an attractive design principle in medicinal chemistry.

Novel C3-Methylene-Bridged Indole Derivatives with and without Substituents at N1: The Influence of Substituents on Their Hemolytic, Cytoprotective, and Antimicrobial Activity.

Alkaloids are natural compounds useful as scaffolds for discovering new bioactive molecules. This study utilized alkaloid gramine to synthesize two groups of C3-substituted indole derivatives, which were either functionalized at N1 or not. The compounds were characterized by spectroscopic methods. The protective effects of the new compounds against in vitro oxidative hemolysis induced by standard oxidant 2,2'-azobis(2-amidinopropane dihydro chloride (AAPH) on human erythrocytes as a cell model were investigated. Additionally, the compounds were screened for antimicrobial activity. The results indicated that most of the indole derivatives devoid of the N1 substitution exhibited strong cytoprotective properties. The docking studies supported the affinities of selected indole-based ligands as potential antioxidants. Furthermore, the derivatives obtained exhibited potent fungicidal properties. The structures of the eight derivatives possessing indole moiety bridged to the imidazole-, benzimidazole-, thiazole-, benzothiazole-, and 5-methylbenzothiazoline-2-thiones were determined by X-ray diffraction. The C=S bond lengths in the thioamide fragment pointed to the involvement of zwitterionic structures of varying contribution. The predominance of zwitterionic mesomers may explain the lack of cytoprotective properties, while steric effects, which limit multiple the hydrogen-bond acceptor properties of a thione sulfur, seem to be responsible for the high hemolytic activity.

Fluorescent Labeling of a Target Protein with an Alkyl Diazirine Photocrosslinker Bearing a Cinnamate Moiety.

A novel fluorogenic alkyl diazirine photocrosslinker bearing an o-hydroxycinnamate moiety has been developed for identification of the targets of bioactive molecules. The o-hydroxycinnamate moiety can be converted to the corresponding 7-hydroxycoumarin derivative, which should be created on the interacting site within the photocaptured target protein. The label yield and fluorescence intensity have been immensely improved in comparison with our previous aromatic crosslinkers to facilitate target identification in small quantities.

Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape

Epicardial adipose tissue (EAT) is a unique fat depot located around the heart, intimately associated with the myocardium and coronary arteries. The secretion of bioactive molecules and their interaction with neighbouring cardiac tissues makes it an active organ with important implications in cardiovascular health and disease. In recent years, omics technologies have provided valuable insights into the molecular characteristics and functional relevance of EAT in patients with coronary atherosclerosis, myocardial infarction, atrial fibrillation and associated metabolic disorders. This review aims to summarize the current understanding of EAT biology through the lens of genomics, transcriptomics, proteomics and lipidomics approaches. We discuss key findings from omics studies on EAT, including gene expression profiles, metabolic activity, signalling pathways and regulatory network, in order to explore in depth the disease mechanisms, possible therapeutic strategies, and cardiovascular risk assessment. Further advances in this field and integrating data from multiple omics platforms hold promise for unlocking personalized cardiometabolic profiles with EAT as a possible biomarker and therapeutic target in cardiovascular disease.

Asymmetric Transfer Hydrogenation of Stable NH Imines for the Synthesis of Enantiopure α‐Chiral Primary Amines

Asymmetric Transfer Hydrogenation of Stable <scp>NH</scp> Imines for the Synthesis of Enantiopure <scp>α‐Chiral</scp> Primary Amines

Photoinduced Perfluoroalkyloximation of Alkenes with Simple Perfluoroalkyl Halides

Photoinduced Perfluoroalkyloximation of Alkenes with Simple Perfluoroalkyl Halides

Recent advances, challenges and functional applications of protein glycosylation modification in food industry

SummaryProtein glycosylation modification is an effective way to enhance the functional properties of natural proteins. This study aims to explore the preparation of glycosylation products (PPCs) through the Maillard reaction or enzymatic glycosylation using transglutaminase. The study discusses the advantages and disadvantages of preparing PPCs using dry heat, wet heat, and enzymatic glycosylation, as well as factors influencing the glycosylation process. Compared to natural proteins, PPCs demonstrate superior functional properties, including solubility, viscosity, emulsifying ability, gelling ability, thermal stability, antioxidant activity, and antibacterial activity. With improved functional performance, PPCs have broad application prospects as raw materials in food processing. For example, PPCs can be used as antioxidants, emulsifiers, gelling agents, and carriers for various bioactive molecules in the food industry. In the pharmaceutical field, PPCs are expected to serve as contrast agents and dressings. Furthermore, the application of PPCs in food processing should also consider specific processing requirements to achieve the intended enhancement of glycosylated protein functionality.

Developing a gel-col heterogeneous network hydrogel scaffold for tissue-engineered skin with enhanced basement membrane formation

Tissue-engineered skin is constructed utilizing biocompatible matrix materials as scaffolds, and incorporating human epidermal keratinocytes (HEKs), dermal fibroblasts (HDFs), and bioactive molecules, addressing clinical issues such as skin graft rejection and donor scarcity. Conventional fabrication methods of tissue-engineered skin typically rely on homogeneous single-network scaffolds, which may not adequately address the distinct requirements of epidermal and dermal cells or the critical formation of the basement membrane, potentially impacting the development and functional integrity of the skin tissue. Cell culture studies employing GelMA hydrogels of varied concentrations have elucidated that epidermal cells exhibit increased viability on scaffolds with higher concentrations (15 %), whereas fibroblasts show increased proliferation within scaffolds of lower concentrations (5 %). Consequently, we have engineered a GelMA-collagen (Gel-Col) hydrogel scaffold with a heterogeneous network of dense and sparse matrices, conducive to the growth of both fibroblasts and epidermal cells. Culturing epidermal cells on this innovative scaffold, coupled with histological section staining, RT-PCR, and Western blot analyses, has demonstrated that the scaffold significantly enhances cellular adhesion and promotes the development of the epidermal basement membrane compared to single-network hydrogels. Mouse wound transplantation experiments have further confirmed the scaffold’s effectiveness in accelerating wound repair, supporting the development of the basement membrane, and enhancing epidermal regeneration. This research provides a reference for constructing tissue-engineered skin that more precisely emulates the intricate architecture and cellular dynamics of natural skin, propelling the advancement of tissue-engineered skin grafts in the clinical treatment of skin injuries.

Factors affecting the production of sugarcane yield and sucrose accumulation: suggested potential biological solutions.

Environmental stresses are the main constraints on agricultural productivity and food security worldwide. This issue is worsened by abrupt and severe changes in global climate. The formation of sugarcane yield and the accumulation of sucrose are significantly influenced by biotic and abiotic stresses. Understanding the biochemical, physiological, and environmental phenomena associated with these stresses is essential to increase crop production. This review explores the effect of environmental factors on sucrose content and sugarcane yield and highlights the negative effects of insufficient water supply, temperature fluctuations, insect pests, and diseases. This article also explains the mechanism of reactive oxygen species (ROS), the role of different metabolites under environmental stresses, and highlights the function of environmental stress-related resistance genes in sugarcane. This review further discusses sugarcane crop improvement approaches, with a focus on endophytic mechanism and consortium endophyte application in sugarcane plants. Endophytes are vital in plant defense; they produce bioactive molecules that act as biocontrol agents to enhance plant immune systems and modify environmental responses through interaction with plants. This review provides an overview of internal mechanisms to enhance sugarcane plant growth and environmental resistance and offers new ideas for improving sugarcane plant fitness and crop productivity.

Preparation and evaluation of decellularized epineurium as an anti-Adhesive biofilm in peripheral nerve repair

Preparation and evaluation of decellularized epineurium as an anti-Adhesive biofilm in peripheral nerve repair

Highly scalable and robust ribbon-like coordination polymer as green catalyst for Hantzsch condensation in synthesis of DHPs and bioactive drug molecule

Ribbon-like coordination polymers (CP) represents a highly unexplored innovative class of metal-coordination network. Herein, we have developed a highly scalable and chemically robust (pH = 3–10 stable) ribbon-like CP [{Cu(Pim)(L)(H2O)·H2O}]n(1) following a complete environment-friendly green synthesis route. Considering the presence of surface flanked labile coordinated water molecules and their appealing correlation with one-dimensional structural characteristics, such sort of ribbon-like CP was explored for the first time as excellent heterogeneous surface catalyst for largely unexplored three-component Hantzsch condensation for synthesis of different classes of dihydropyridine (DHP). Moreover, 1 is employed to synthesize bio-responsive drug ‘Ethidine’ (possessing high anti-oxidant and anticarcinogenic properties) characterized with Single Crystal X-ray Diffraction (SCXRD) analysis. Several DHP-based products are also analysed through in-depth SCXRD analysis. This report inaugurates the usage of a Cu(II) based ribbon-like CPs as heterogeneous surface catalyst following environmentally benign manner for synthesis of bioactive DHPs and Drugs.

A General Iron-Catalyzed Decarboxylative Oxygenation of Aliphatic Carboxylic Acids.

We report an iron-catalyzed decarboxylative C(sp3)-O bond-forming reaction under mild, base-free conditions with visible light irradiation. The transformation uses readily available and structurally diverse carboxylic acids, iron photocatalyst, and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) derivatives as oxygenation reagents. The process exhibits a broad scope in acids possessing a wide range of stereoelectronic properties and functional groups. The developed reaction was applied to late-stage oxygenation of a series of bio-active molecules. The reaction leverages the ability of iron complexes to generate carbon-centered radicals directly from carboxylic acids by photoinduced carboxylate-to-iron charge transfer. Kinetic, electrochemical, EPR, UV-Vis, HRMS and DFT studies revealed that TEMPO has a triple role in the reaction: as an oxygenation reagent, an oxidant to turn over the Fe-catalyst, and an internal base for the carboxylic acid deprotonation. The obtained TEMPO adducts represent versatile synthetic intermediates that were further engaged in C-C and C-heteroatom bond-forming reactions using commercial organo-photocatalysts and nucleophilic reagents.

ClassyPose: A Machine‐Learning Classification Model for Ligand Pose Selection Applied to Virtual Screening in Drug Discovery

Determining the target‐bound conformation of a drug‐like molecule is a crucial step in drug design, as it affects the outcome of virtual screening (VS), and paves the way for hit‐to‐lead and lead optimization. While most docking programs usually manage to produce at least a near‐native pose for a bioactive molecule inside its binding pocket, their integrated classical scoring functions (SFs) generally fail to prioritize this pose. Many studies have been carried out to tackle this SF problem, offering multiple pose refinement and/or classification methods, albeit with limitations. This study presents a new support vector machine model for pose classification, called “ClassyPose”, which predicts the probability that a receptor‐bound ligand conformation could be near‐native, without any additional pose optimization step. Trained on protein‐ligand extended connectivity features extracted from over 21 600 crystal and docking poses of diverse ligands, this model outperformed other machine‐learning algorithms and three existing SFs in terms of docking power, identifying the native ligand pose as top‐ranked solution for more than 90% of entries in two test sets. It also achieved high specificity (above 0.96), and improved VS performance when used for pose selection. This efficient, user‐friendly tool and all related data are available at https://github.com/vktrannguyen/Classy_Pose.

Isolation of Extracellular Vesicles from Agri-Food Wastes: A Novel Perspective in the Valorization of Agri-Food Wastes and By-Products.

Agri-food wastes generated by industrial food processing are valorized through the extraction of biomolecules to obtain value-added products useful for various industrial applications. In the present review, we describe the valuable by-products and bioactive molecules that can be obtained from agricultural wastes and propose extracellular vesicles (EVs) as innovative nutraceutical and therapeutic compounds that could be derived from agriculture residues. To support this idea, we described the general features and roles of EVs and focused on plant-derived extracellular vesicles (PDEVs) that are considered natural carriers of bioactive molecules and are involved in intercellular communication between diverse kingdoms of life. Consistently, PDEVs exert beneficial effects (anti-inflammatory, anti-tumor, and immune-modulatory) on mammalian cells. Although this research field is currently in its infancy, in the near future, the isolation of EVs and their use as nutraceutical tools could represent a new and innovative way to valorize waste from the agri-food industry in an ecofriendly way.

The effect of macrophages and their exosomes in ischemic heart disease.

Ischemic heart disease (IHD) is a leading cause of disability and death worldwide, with immune regulation playing a crucial role in its pathogenesis. Various immune cells are involved, and as one of the key immune cells residing in the heart, macrophages play an indispensable role in the inflammatory and reparative processes during cardiac ischemia. Exosomes, extracellular vesicles containing lipids, nucleic acids, proteins, and other bioactive molecules, have emerged as important mediators in the regulatory functions of macrophages and hold promise as a novel therapeutic target for IHD. This review summarizes the regulatory mechanisms of different subsets of macrophages and their secreted exosomes during cardiac ischemia over the past five years. It also discusses the current status of clinical research utilizing macrophages and their exosomes, as well as strategies to enhance their therapeutic efficacy through biotechnology. The aim is to provide valuable insights for the treatment of IHD.

Mass spectrometry and Nuclear magnetic resonance spectroscopy profiles of red and pink Rhododendron flower petals establish them as rich sources of bioactive secondary metabolites

AbstractRhododendron petals are considered high‐value owing to their commercial utility, national/state flower status in certain countries, and bioactive potential from recent studies. Profiling and quantitative analysis of the bioactive metabolites would evaluate if they can be natural sources. This study is focused on the comprehensive profiling of secondary metabolites in the hot aqueous petal extracts of Red and Pink Rhododendron flowers (Rhododendron arboreum and Rhododendron campanulatum) using separation and fragmentation patterns from mass spectrometry (MS) (gas chromatography‐MS and liquid chromatography‐tandem MS) and chemical shifts from proton‐nuclear magnetic resonance spectroscopy. The complementary analytical platforms highlighted the petals to be rich in promising bioactive molecules such as quinic acid, chlorogenic acid (caffeoyl quinic acid), protocatechuic acid, coumaroyl quinic acids, catechin, epigallocatechin, and shikimic acid. The analysis also reflected the activity of shikimic acid, phenolic acid, and flavonoid biosynthetic pathways in Rhododendron flowers. These metabolites are well reported for their bioactive potential as anti‐oxidative, anti‐viral, anti‐cancerous, anti‐diabetic, anti‐inflammatory, etc. While the quantitative and multivariate analysis showed variations in the levels of phenolic acids and flavonoids, it is established that red and pink Rhododendron flower petals are a rich source of bioactive phytochemicals of interest to the phytochemical Industry.