Bioactive Molecules Research Articles

Studies of Impact on Bioactive Molecules of SB2 Isolate and their PGPR Activities from the Marine Environment

Marine microbes are important sources for recovering bioactive substances. One of the marine isolates, SB2, used a variety of media, with tryptic soy broth showing the best growth and yellow coloring. The largest amount of biomass was produced after 72 hours when the strain SB2 was cultured on glucose, molasses, and peptone, a yeast extract containing carbon and nitrogen sources. Yellow pigment must be extracted using methanol, and the isolate SB2 produced the most of this color. At a concentration of 100 g ml-1 of several bacterial pathogens, the recovered pigment from the SB2 isolate exhibited antibacterial action. The maximum production of IAA and GA is shown in TS broth, which is additionally augmented by the siderophore synthesis of catechol and salicylate. The SB2 also produces IAA and GA. In contrast, the highest level of ACC deaminase activity was found in nutrient broth. Due to the generation of pigment, the strain SB2 may be essential for Plant Growth Promoting Rhizobacteria (PGPR) and antibacterial properties.

Ir-catalyzed photoredox cascade radical annulation reactions toward phosphinimides bearing quaternary carbon center at room temperature

Organophosphorus aza-heterocycles are widely found in the framework of numerous bioactive molecules, functional materials, and commercially available drugs. We report herein a photoredox-catalyzed radical addition cascade annulation sequence of acyclic phosphinimides with a variety of organohalides under mild and external oxidant-free reaction conditions. A wide range of functionalized phosphinimides bearing a quaternary carbon center could be efficiently and selectively produced by employing diverse radical precursors, including sulfonyl, perfluoroalkyl, trichloromethyl, and carbonyl halides, under mild reaction conditions.

From the gut to the brain: the long journey of phenolic compounds with neurocognitive effects.

The human gut microbiota is a complex community of micro-organisms that play a crucial role in maintaining overall health. Recent research has shown that gut microbes also have a profound impact on brain function and cognition, leading to the concept of the gut-brain axis. One way in which the gut microbiota can influence the brain is through the bioconversion of polyphenols to other bioactive molecules. Phenolic compounds are a group of natural plant metabolites widely available in the human diet, which have anti-inflammatory and other positive effects on health. Recent studies have also suggested that some gut microbiota-derived phenolic metabolites may have neurocognitive effects, such as improving memory and cognitive function. The specific mechanisms involved are still being studied, but it is believed that phenolic metabolites may modulate neurotransmitter signaling, reduce inflammation, and enhance neural plasticity. Therefore, to exert a protective effect on neurocognition, dietary polyphenols or their metabolites must reach the brain, or act indirectly by producing an increase in bioactive molecules such as neurotransmitters. Once ingested, phenolic compounds are subjected to various processes (eg, metabolization by gut microbiota, absorption, distribution) before they cross the blood-brain barrier, perhaps the most challenging stage of their trajectory. Understanding the role of phenolic compounds in the gut-brain axis has important implications for the development of new therapeutic strategies for neurological and psychiatric disorders. By targeting the gut microbiota and its production of phenolic metabolites, it may be possible to improve brain function and prevent cognitive decline. In this article, the current state of knowledge on the endogenous generation of phenolic metabolites by the gut microbiota and how these compounds can reach the brain and exert neurocognitive effects was reviewed.

Strategies Employed to Design Biocompatible Metal Nanoparticles for Medical Science and Biotechnology Applications.

The applicability of nanomaterials has evolved in biomedical domains thanks to advances in biocompatibility strategies and the mitigation of cytotoxic effects, allowing diagnostics, imaging, and therapeutic approaches. The application of nanoparticles (NP), particularly metal nanoparticles (mNPs), such as gold (Au) and silver (Ag), includes inherent challenges related to the material characteristics, surface modification, and bioconjugation techniques. By tailoring the surface properties through appropriate coating with biocompatible molecules or functionalization with active biomolecules, researchers can reach a harmonious interaction with biological systems or samples (mostly fluids or tissues). Thus, this review highlights the mechanisms associated with the obtention of biocompatible mNP and presents a comprehensive overview of methods that facilitate safe and efficient production. Therefore, we consider this review to be a valuable resource for all researchers navigating this dynamic field.

Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain.

Neuropathic pain (NPP) remains a clinically challenging condition, driven by the activation of spinal astrocytes and the complex release of inflammatory mediators. This study aimed to examine the roles of Rab8a and SNARE complex proteins in activated astrocytes to uncover the underlying mechanisms of NPP. The research was conducted using a rat model with chronic constriction injury (CCI) of the sciatic nerve and primary astrocytes treated with lipopolysaccharide. Enhanced expression of Rab8a was noted specifically in spinal dorsal horn astrocytes through immunofluorescence. Electron microscopy observations showed increased vesicular transport and exocytic activity in activated astrocytes, which was corroborated by elevated levels of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α detected through quantitative PCR. Western blot analyses confirmed significant upregulation of Rab8a, VAMP2, and Syntaxin16 in these cells. Furthermore, the application of botulinum neurotoxin type A (BONT/A) reduced the levels of vesicle transport-associated proteins, inhibiting vesicular transport in activated astrocytes. These findings suggest that the Rab8a/SNARE pathway in astrocytes enhances vesicle transport and anchoring, increasing the secretion of bioactive molecules that may play a crucial role in the pathophysiology of NPP. Inhibiting this pathway with BONT/A offers a novel therapeutic target for managing NPP, highlighting its potential utility in clinical interventions.

Targeting tumor‑associated macrophages: Critical players in tumor progression and therapeutic strategies (Review).

Tumor‑associated macrophages (TAMs) are essential components of the tumor microenvironment (TME) and display phenotypic heterogeneity and plasticity associated with the stimulation of bioactive molecules within the TME. TAMs predominantly exhibit tumor‑promoting phenotypes involved in tumor progression, such as tumor angiogenesis, metastasis, immunosuppression and resistance to therapies. In addition, TAMs have the potential to regulate the cytotoxic elimination and phagocytosis of cancer cells and interact with other immune cells to engage in the innate and adaptive immune systems. In this context, targeting TAMs has been a popular area of research in cancer therapy, and a comprehensive understanding of the complex role of TAMs in tumor progression and exploration of macrophage‑based therapeutic approaches are essential for future therapeutics against cancers. The present review provided a comprehensive and updated overview of the function of TAMs in tumor progression, summarized recent advances in TAM‑targeting therapeutic strategies and discussed the obstacles and perspectives of TAM‑targeting therapies for cancers.

Base‐Promoted Selective Synthesis of Alkynyl Sulfides via C−S Bond Cleavage of Alkynyl Sulfonium Salts

AbstractAn effective one‐pot approach has been devised for the selective synthesis of alkynyl sulfides through the cleavage of C−S bonds in alkynyl sulfonium salts. This method involves a base‐promoted nucleophilic ring‐opening and desulfurization pathway, enabling the efficient preparation of diverse alkynyl sulfide compounds. The reaction demonstrates excellent tolerance to various functional groups and proves applicable to the late‐stage functionalization of bioactive molecules and pharmaceuticals. Moreover, the practicality of this method has been underscored through scale‐up reaction and modification of alkynyl sulfide products.

Synthetic Protocols, Structural Activity Relationship, and Biological Activity of Piperazine and its Derivatives.

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs was also highlighted to provide a good understanding to researchers for future research on piperazines.

Cheminformatics approach to identify andrographolide derivatives as dual inhibitors of methyltransferases (nsp14 and nsp16) of SARS-CoV-2

The Covid-19 pandemic outbreak has accelerated tremendous efforts to discover a therapeutic strategy that targets severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control viral infection. Various viral proteins have been identified as potential drug targets, however, to date, no specific therapeutic cure is available against the SARS-CoV-2. To address this issue, the present work reports a systematic cheminformatic approach to identify the potent andrographolide derivatives that can target methyltransferases of SARS-CoV-2, i.e. nsp14 and nsp16 which are crucial for the replication of the virus and host immune evasion. A consensus of cheminformatics methodologies including virtual screening, molecular docking, ADMET profiling, molecular dynamics simulations, free-energy landscape analysis, molecular mechanics generalized born surface area (MM-GBSA), and density functional theory (DFT) was utilized. Our study reveals two new andrographolide derivatives (PubChem CID: 2734589 and 138968421) as natural bioactive molecules that can form stable complexes with both proteins via hydrophobic interactions, hydrogen bonds and electrostatic interactions. The toxicity analysis predicts class four toxicity for both compounds with LD50 value in the range of 500–700 mg/kg. MD simulation reveals the stable formation of the complex for both the compounds and their average trajectory values were found to be lower than the control inhibitor and protein alone. MMGBSA analysis corroborates the MD simulation result and showed the lowest energy for the compounds 2734589 and 138968421. The DFT and MEP analysis also predicts the better reactivity and stability of both the hit compounds. Overall, both andrographolide derivatives exhibit good potential as potent inhibitors for both nsp14 and nsp16 proteins, however, in-vitro and in vivo assessment would be required to prove their efficacy and safety in clinical settings. Moreover, the drug discovery strategy aiming at the dual target approach might serve as a useful model for inventing novel drug molecules for various other diseases.

A review of natural products and small-molecule therapeutics acting on central nervous system malignancies: Approaches for drug development, targeting pathways, clinical trials, and challenges.

In 2021, the World Health Organization released the fifth edition of the central nervous system (CNS) tumor classification. This classification uses histopathology and molecular pathogenesis to group tumors into more biologically and molecularly defined entities. The prognosis of brain cancer, particularly malignant tumors, has remained poor worldwide, approximately 308,102 new cases of brain and other CNS tumors were diagnosed in the year 2020, with an estimated 251,329 deaths. The cost and time-consuming nature of studies to find new anticancer agents makes it necessary to have well-designed studies. In the present study, the pathways that can be targeted for drug development are discussed in detail. Some of the important cellular origins, signaling, and pathways involved in the efficacy of bioactive molecules againstCNS tumorigenesis or progression, as well as prognosis and common approaches for treatment of different types of brain tumors, are reviewed. Moreover, different study tools, including cell lines, in vitro, in vivo, and clinical trial challenges, are discussed. In addition, in this article, natural products as one of the most important sources for finding new chemotherapeutics were reviewed and over 700 reported molecules with efficacy against CNS cancer cells are gathered and classified according to their structure. Based on the clinical trials that have been registered, very few of these natural or semi-synthetic derivatives have been studied in humans. The review can help researchers understand the involved mechanisms and design new goal-oriented studies for drug development against CNS malignancies.

Methyl Pyruvate Oxime as a Carbonyl Synthon: Synthesis of Ureas, Carbamates, Thiocarbamates, and Anilides.

A new strategy for the synthesis of unsymmetrical ureas, carbamates, thiocarbamates, and anilides was developed with methyl pyruvate oxime as the carbonyl synthon. The intrinsic reactivity of the reagent enabled consecutive disubstitution involving direct amidation and one-pot deoximative substitution with various nucleophiles. The utility of the method was demonstrated with the synthesis of bioactive molecules.

Overview of the distinctive characteristics of strawberry, raspberry, and blueberry in berries, berry wines, and berry spirits.

Red berries have gained popularity as functional and nutritious food due to their health benefits, leading to increased consumer demand and higher production, totaling over 11,000ktons for strawberries, raspberries, and blueberries combined in 2021. Nutritionally, strawberries, raspberries, and blueberries present high levels of vitamin C (9.7-58.8mg/100g dry weight [dw]), folates (6-24µg/100g dw), and minerals (96-228mg/100g dw). Due to their perishable nature, producers have utilized alcoholic fermentation to extend their shelf life, not only increasing the lifespan of red berries but also attracting consumers through the production of novel beverages. Strawberry, blueberry, and raspberry wines possess low alcohol (5.5-11.1% v/v), high acidity (3.2-17.6g/L), and interesting bioactive molecules such as phenolic compounds, carotenoids, polysaccharides, and melatonin. Distillation holds tremendous potential for reducing food waste by creating red berry spirits of exceptional quality. Although research on red berry spirits is still in the early stages, future studies should focus on their production and characterization. By incorporating these factors, the production chain would become more sustainable, profitable, and efficient by reducing food waste, capitalizing on consumer acceptance, and leveraging the natural health-promoting characteristics of these products. Therefore, this review aims to provide a comprehensive overview of the characteristics of strawberry, blueberry, and red raspberry in berries, wines, and spirits, with a focus on their chemical composition and production methods.

Fabrication of hydrophobic drug-loaded Zeolitic Imidazolate Framework-8 (ZIF-8) for enhanced anti-bacterial activity

Current study presents a novel approach for constructing small hydrophobic biomolecules embedded within zeolitic imidazolate framework-8 (ZIF-8) with exceptional antibacterial properties. In this method, ZIF-8 is synthesized from zinc acetate and 2-methylimidazole in the presence or absence of small hydrophobic bioactive molecules like rutin, rosmarinic acid, and morin. Scanning electron microscopy (SEM) analysis reveals that the synthesized ZIF-8 nanoparticles exhibit mostly hexagonal shape with size 200 nm which is further increased upon drug encapsulation. The synthesis of ZIF-8 and drug-loaded ZIF-8 is confirmed through FTIR, UV–vis spectroscopy, XRD, TGA, and EDX analyses. Zeta potential measurements show values ranging from -14.5 to -23.97 mV for both ZIF-8 and drug-loaded ZIF-8 nanoparticles. The drug loading content is determined to be 5 %, 9 %, and 16 % for morin, rutin, and rosmarinic acid, respectively. All the drug-loaded ZIF-8 formulations exhibit a pH-dependent drug release pattern, with maximal drug release observed at lower pH levels. Most importantly, these formulations demonstrate potent antibacterial activity against both Gram-positive (Enterococcus faecalis and Bacillus subtilis) and Gram-negative (Escherichia coli) bacterial strains. Specifically, ZIF-8/RUT exhibit maximum zone of inhibition (ZOI ∼ 51 mm) against all tested bacterial strains. ZIF-8/MOR and ZIF-8/RUT exhibit MIC values ranging from 2.0 to 3.0 mg/mL and MBC values from 6 to 9 mg/mL against all the tested bacteria. Among the formulations, ZIF-8/MOR and ZIF-8/RUT exhibit synergistic antibacterial effect, whereas ZIF-8/RMA possess less antibacterial potency against all the tested bacteria and mostly exhibit additive effect. Our findings suggest that these newly developed nano-formulations hold potential for the creation of highly effective antibacterial agents.

PH‐Responsive Virus‐Based Colloidal Crystals for Advanced Material Platforms

AbstractBacteriophages have a well‐defined nanoscale size, shape, and surface chemistry, making them promising candidates for creating advanced biomaterials for applications including biocatalysis, drug delivery, and biosensing. This study demonstrates the self‐assembly of the ≈29 nm diameter bacteriophage Qbeta (Qubevirus durum) with the synthetic polycation, poly [2‐(methacryloyloxy)ethyl] trimethylammonium chloride (pMETAC), into compartmentalized colloidal crystals. The pH and the polymer chain length tune their self‐assembly and the resulting structure, with the potential for further chemical modification or loading with bioactive molecules. Small angle X‐ray scattering (SAXS), multi‐angle dynamic light scattering (DLS), and atomic force microscopy (AFM) are used for studying the Qbeta self‐assembly into the geometrically ordered aggregates. The suprastructures form at pH > 7.0 and disassemble at pH < 7.0. Zeta potential measurements and X‐ray photoelectron spectroscopy (XPS) show pMETAC adsorption onto the negatively charged Qbeta surface. The colloidal crystal formation is achieved without chemically modifying the Qbeta surface. Additionally, the Qbeta/pMETAC suprastructures can be easily separated from the suspension as macroscopic aggregate, maintaining their activity. Their simple preparation allows for large‐scale production of advanced materials in food and health science applications and nanotechnology. The insights from this study will further advance the tailored design and production of novel colloidal materials.

Differential expression profiles and bioinformatics analysis of tRNA-derived small RNAs in epicardial fat of patients with atrial fibrillation

The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly–CCC–003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.

Phytochemicals, Herbal Extracts, and Dietary Supplements for Metabolic Disease Management.

Comprehensive and effective care techniques have become essential due to the global epidemic dimensions of metabolic disorders, including diabetes, obesity, and cardiovascular ailments. Recent research highlights the potential of dietary supplements, herbal extracts, and phytochemicals in treating metabolic diseases. This abstract conveys the current state of the science in this field by highlighting these findings' underlying mechanisms and potential therapeutic applications. Plant-based diets contain naturally occurring bioactive molecules termed phytochemicals, which have shown promise in treating various metabolic illnesses. Examples include curcumin, flavonoids, and polyphenols' insulin-sensitizing, antioxidant, and antiinflammatory properties. Herbal extracts, derived from ancient medicinal herbs, have been used by people for years to treat a wide range of ailments. Recent studies have shown the efficacy of these strategies in improving lipid profiles, glucose metabolism, and overall cardiovascular health. Omega-3 fatty acids, vitamins, and minerals are just a few of the numerous nutritional supplements that are critical to metabolic health. These vitamins improve insulin sensitivity, regulate blood sugar, and decrease inflammation. Probiotics and prebiotics also affect the gut flora, which significantly affects metabolic function. These natural medicines' ability to treat metabolic diseases either by themselves or in combination with conventional medical interventions. However, when using it therapeutically, one must consider the differences in doses, individual responses, and bioavailability. The article concludes that phytochemicals, plant extracts, and food supplements offer a promising avenue for the management of metabolic illnesses. Comprehensive research, including clinical studies, is needed to ascertain their safety and efficacy characteristics. When added to treatment strategies, these natural therapies could be helpful supplements that improve overall health and the quality of life among individuals with metabolic diseases. Naringenin, a citrus flavonoid, can potentially prevent kidney injury in hyperuricemia by reducing uric acid, inflammation, apoptosis, DNA damage, and activating antioxidants. Further research and professional consultation are essential. Factors contributing to metabolic diseases, current approaches to management nutritional approaches for managing obesityassociated metabolic impairments in the liver and small intestine, and nutritional approaches for managing obesity-associated metabolic dysregulation are also explained briefly.

Role of Extracellular Vesicles Derived Non-coding RNAs in Diabetic Kidney Disease

Diabetic kidney disease (DKD), a metabolic related syndrome characterized by abnormal glomerular filtration rate (GFR), proteinuria and renal microangiopathy, is one of the most common form of chronic kidney diseases (CKD), whereas extracellular vesicles (EVs) have been recently evidenced as a novel cell communication player in DKD occurrence and progress via releasing various of bioactive molecules, including proteins, lipids and especially RNA, among which noncoding RNAs (including miRNAs, lncRNAs and circRNAs) are the major regulators. In current review, we summarized the mechanistic role of EVs in DKD according to biology function classifications, including inflammation and oxidative stress, epithelial–mesenchymal transition (EMT), cell death and extracellular matrix (ECM) deposition. Furthermore, potential clinical applications based on these non-coding RNA have also been reviewed, thereby expecting possible therapeutic insights in clinical practice.

Catalytic Asymmetric Synthesis of Chiral α,α-Dialkyl Aminonitriles via Reaction of Cyanoketimines.

Chiral aminonitriles not only are broadly useful building blocks but also increasingly appear as structural motifs in bioactive molecules and pharmaceuticals. The catalytic asymmetric synthesis of chiral aminonitriles, therefore, has been intensively investigated, as reflected in numerous reports of catalytic asymmetric Strecker reactions. Despite such great progress, the catalytic asymmetric synthesis of chiral α,α-dialkyl aminonitriles in a highly selective and efficient manner is still a formidable challenge. Here, we report a new approach for the catalytic asymmetric synthesis of chiral α,α-dialkyl aminonitriles via reaction of cyanoketimines with enals. We demonstrate that this reaction could be carried out with as low as 20 ppm catalyst loading.

Synthesis of 18F‐labeled Aryl Trifluoromethyl Sulfones, ‐Sulfoxides, and ‐Sulfides for Positron Emission Tomography

Positron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is particularly true for the highly desired radiolabeling of compounds bearing [18F]CF3‐groups. For instance, S(O)nCF3‐groups (n = 0, 1, 2) serve as structural motif in a range of biologically active compounds, but their radiosynthesis remains largely unprecedented (for n = 1, 2). Herein, we describe general methods for the radiosynthesis of 18F‐labeled aryl trifluoromethyl sulfones, ‐sulfoxides, and –sulfides. All three methods are operationally straightforward, start from widely available precursors, i.e., sulfonyl fluorides and thiophenols, and make use of the recently established [18F]Ruppert‐Prakash reagent. Further, the syntheses display good functional group tolerance as demonstrated by the 18F‐labeling of more than 40 compounds. The applicability of the new method is demonstrated by the radiolabeling of three bioactive molecules, optionally to be used as PET tracers. In a broader context, this work presents a substantial expansion of the chemical space of radiofluorinated structural motifs to be used for the development of new PET tracers.

Synthesis of 18F-labeled Aryl Trifluoromethyl Sulfones, -Sulfoxides, and -Sulfides forPositron Emission Tomography.

Positron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is particularly true for the highly desired radiolabeling of compounds bearing [18F]CF3-groups. For instance, S(O)nCF3-groups (n = 0, 1, 2) serve as structural motif in a range of biologically active compounds, but their radiosynthesis remains largely unprecedented (for n = 1, 2). Herein, we describe general methods for the radiosynthesis of 18F-labeled aryl trifluoromethyl sulfones, -sulfoxides, and -sulfides. All three methods are operationally straightforward, start from widely available precursors, i.e., sulfonyl fluorides and thiophenols, and make use of the recently established [18F]Ruppert-Prakash reagent. Further, the syntheses display good functional group tolerance as demonstrated by the 18F-labeling of more than 40 compounds. The applicability of the new method is demonstrated by the radiolabeling of three bioactive molecules, optionally to be used as PET tracers. In a broader context, this work presents a substantial expansion of the chemical space of radiofluorinated structural motifs to be used for the development of new PET tracers.