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Molecules (Basel, Switzerland) Jun 2024This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based...
BACKGROUND
This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties.
METHOD
Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria.
RESULTS
The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability.
CONCLUSIONS
The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.
Topics: Liposomes; Surface-Active Agents; Amino Acids; Anti-Infective Agents; Molecular Docking Simulation; Anesthetics; Drug Compounding; Microbial Sensitivity Tests
PubMed: 38930908
DOI: 10.3390/molecules29122843 -
Molecules (Basel, Switzerland) Jun 2024The diketopyrrolopyrrole (DPP) unit represents one of the building blocks more widely employed in the field of organic electronics; in most of the reported DPP-based...
The diketopyrrolopyrrole (DPP) unit represents one of the building blocks more widely employed in the field of organic electronics; in most of the reported DPP-based small molecules, this unit represents the electron acceptor core symmetrically coupled to donor moieties, and the solubility is guaranteed by functionalizing lactamic nitrogens with long and branched alkyl tails. In this paper, we explored the possibility of modulating the solubility by realizing asymmetric DPP derivatives, where the molecular structure is extended in just one direction. Four novel derivatives have been prepared, characterized by a common dithyenil-DPP fragment and functionalized on one side by a thiophene unit linked to different auxiliary electron acceptor groups. As compared to previously reported symmetric analogs, the novel dyes showed an increased solubility in chloroform and proved to be soluble in THF as well. The novel dyes underwent a thorough optical and electrochemical characterization. Electronic properties were studied at the DFT levels. All the dyes were used as active layers in organic field effect transistors, showing balanced charge transport properties.
PubMed: 38930874
DOI: 10.3390/molecules29122805 -
Molecules (Basel, Switzerland) Jun 2024Hydrogen generation by photocatalytic water-splitting holds great promise for addressing the serious global energy and environmental crises, and has recently received...
Hydrogen generation by photocatalytic water-splitting holds great promise for addressing the serious global energy and environmental crises, and has recently received significant attention from researchers. In this work, a method of assembling GeC/MXY (M = Zr, Hf; X, Y = S, Se) heterojunctions (HJs) by combining GeC and MXY monolayers (MLs) to construct direct Z-scheme photocatalytic systems is proposed. Based on first-principles calculations, we found that all the GeC/MXY HJs are stable van der Waals (vdW) HJs with indirect bandgaps. These HJs possess small bandgaps and exhibit strong light-absorption ability across a wide range. Furthermore, the built-in electric field (BIEF) around the heterointerface can accelerate photoinduced carrier separation. More interestingly, the suitable band edges of GeC/MXY HJs ensure sufficient kinetic potential to spontaneously accomplish water redox reactions under light irradiation. Overall, the strong light-harvesting ability, wide light-absorption range, small bandgaps, large heterointerfacial BIEFs, suitable band alignments, and carrier migration paths render GeC/MXY HJs highly efficient photocatalysts for overall water decomposition.
PubMed: 38930861
DOI: 10.3390/molecules29122793 -
Molecules (Basel, Switzerland) Jun 2024The photoelectrochemical (PEC) conversion of organic small molecules offers a dual benefit of synthesizing value-added chemicals and concurrently producing hydrogen (H)....
The photoelectrochemical (PEC) conversion of organic small molecules offers a dual benefit of synthesizing value-added chemicals and concurrently producing hydrogen (H). Ethylene glycol, with its dual hydroxyl groups, stands out as a versatile organic substrate capable of yielding various C1 and C2 chemicals. In this study, we demonstrate that pH modulation markedly enhances the photocurrent of BiVO photoanodes, thus facilitating the efficient oxidation of ethylene glycol while simultaneously generating H. Our findings reveal that in a pH = 1 ethylene glycol solution, the photocurrent density at 1.23 V vs. RHE can attain an impressive 7.1 mA cm, significantly surpassing the outputs in neutral and highly alkaline environments. The increase in photocurrent is attributed to the augmented adsorption of ethylene glycol on BiVO under acidic conditions, which in turn elevates the activity of the oxidation reaction, culminating in the maximal production of formic acid. This investigation sheds light on the pivotal role of electrolyte pH in the PEC oxidation process and underscores the potential of the PEC strategy for biomass valorization into value-added products alongside H fuel generation.
PubMed: 38930848
DOI: 10.3390/molecules29122783 -
Molecules (Basel, Switzerland) Jun 2024The journey of drug discovery (DD) has evolved from ancient practices to modern technology-driven approaches, with Artificial Intelligence (AI) emerging as a pivotal... (Review)
Review
The journey of drug discovery (DD) has evolved from ancient practices to modern technology-driven approaches, with Artificial Intelligence (AI) emerging as a pivotal force in streamlining and accelerating the process. Despite the vital importance of DD, it faces challenges such as high costs and lengthy timelines. This review examines the historical progression and current market of DD alongside the development and integration of AI technologies. We analyse the challenges encountered in applying AI to DD, focusing on drug design and protein-protein interactions. The discussion is enriched by presenting models that put forward the application of AI in DD. Three case studies are highlighted to demonstrate the successful application of AI in DD, including the discovery of a novel class of antibiotics and a small-molecule inhibitor that has progressed to phase II clinical trials. These cases underscore the potential of AI to identify new drug candidates and optimise the development process. The convergence of DD and AI embodies a transformative shift in the field, offering a path to overcome traditional obstacles. By leveraging AI, the future of DD promises enhanced efficiency and novel breakthroughs, heralding a new era of medical innovation even though there is still a long way to go.
Topics: Artificial Intelligence; Humans; Drug Discovery; Drug Design; Drug Development
PubMed: 38930784
DOI: 10.3390/molecules29122716 -
Micromachines Jun 2024In recent years, with the outbreak of the global energy crisis, renewable solar energy has become a focal point of research. However, the utilization efficiency of... (Review)
Review
In recent years, with the outbreak of the global energy crisis, renewable solar energy has become a focal point of research. However, the utilization efficiency of natural photosynthesis (NPS) is only about 1%. Inspired by NPS, artificial photosynthesis (APS) was developed and utilized in applications such as the regeneration of coenzymes. APS for coenzyme regeneration can overcome the problem of high energy consumption in comparison to electrocatalytic methods. Microreactors represent a promising technology. Compared with the conventional system, it has the advantages of a large specific surface area, the fast diffusion of small molecules, and high efficiency. Introducing microreactors can lead to more efficient, economical, and environmentally friendly coenzyme regeneration in artificial photosynthesis. This review begins with a brief introduction of APS and microreactors, and then summarizes research on traditional electrocatalytic coenzyme regeneration, as well as photocatalytic and photo-electrocatalysis coenzyme regeneration by APS, all based on microreactors, and compares them with the corresponding conventional system. Finally, it looks forward to the promising prospects of this technology.
PubMed: 38930759
DOI: 10.3390/mi15060789 -
Microorganisms Jun 2024is a Gram-positive, spore-forming anaerobic bacterial pathogen that causes severe gastrointestinal infection in humans. This review provides background information on... (Review)
Review
is a Gram-positive, spore-forming anaerobic bacterial pathogen that causes severe gastrointestinal infection in humans. This review provides background information on infection and the pathogenesis and toxigenicity of . The risk factors, causes, and the problem of recurrence of disease and current therapeutic treatments are also discussed. Recent therapeutic developments are reviewed including small molecules that inhibit toxin formation, disrupt the cell membrane, inhibit the sporulation process, and activate the host immune system in cells. Other treatments discussed include faecal microbiota treatment, antibody-based immunotherapies, probiotics, vaccines, and violet-blue light disinfection.
PubMed: 38930588
DOI: 10.3390/microorganisms12061206 -
Microorganisms Jun 2024(), a protozoan parasite prevalent in North America, is a significant threat for human health. Given the regulatory role of pyruvate kinase I (PyK I) in glycolytic...
(), a protozoan parasite prevalent in North America, is a significant threat for human health. Given the regulatory role of pyruvate kinase I (PyK I) in glycolytic metabolism flux and ATP generation, PyK I has been considered the target for drug intervention for a long time. In this study, PyK I (BdPyK I) was successfully cloned, expressed, and purified. Polyclonal antibodies were confirmed to recognize the native BdPyK I protein (56 kDa) using Western blotting. AlphaFold software predicted the three-dimensional structure of BdPyK I, and molecular docking with small molecules was conducted to identify potential binding sites of inhibitor on BdPyK I. Moreover, inhibitory effects of six inhibitors (tannic acid, apigenin, shikonin, PKM2 inhibitor, rosiglitazone, and pioglitazone) on BdPyK I were examined under the optimal enzymatic conditions of 3 mM PEP and 3 mM ADP, and significant activity reduction was found. Enzyme kinetics and growth inhibition assays further confirmed the reliability of these inhibitors, with PKM2 inhibitor, tannic acid, and apigenin exhibiting the highest selectivity index as specific inhibitors for . Subsequently, key amino acid residues were mutated in both BdPyK I and Homo sapiens pyruvate kinase I (HPyK I), and two differential amino acid residues (isoleucine and phenylalanine) were identified between HPyK I and BdPyK I through PyK activity detection experiments. These findings lay foundation for understanding the role of PyK I in the growth and development of , providing insights for babesiosis prevention and drug development.
PubMed: 38930523
DOI: 10.3390/microorganisms12061141 -
Microorganisms May 2024Extensive research has been conducted to identify key proteins governing stress responses, virulence, and antimicrobial resistance, as well as to elucidate their...
Extensive research has been conducted to identify key proteins governing stress responses, virulence, and antimicrobial resistance, as well as to elucidate their interactions within . While these proteins hold promise as potential targets for novel strategies to control , given their critical roles in regulating the pathogen's metabolism, additional analysis is needed to further assess their druggability-the chance of being effectively bound by small-molecule inhibitors. In this work, 535 binding pockets of 46 protein targets for known drugs (mainly antimicrobials) were first analyzed to extract 13 structural features (e.g., hydrophobicity) in a ligand-protein docking platform called Molsoft ICM Pro. The extracted features were used as inputs to develop a logistic regression model to assess the druggability of protein binding pockets, with a value of one if ligands can bind to the protein pocket. The developed druggability model was then used to evaluate 23 key proteins from that have been identified in the literature. The following proteins are predicted to be high-potential druggable targets: GroEL, FliH/FliI complex, FliG, FlhB, FlgL, FlgK, InlA, MogR, and PrfA. These findings serve as an initial point for future research to identify specific compounds that can inhibit druggable target proteins and to design experimental work to confirm their effectiveness as drug targets.
PubMed: 38930455
DOI: 10.3390/microorganisms12061073 -
Life (Basel, Switzerland) May 2024Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (, , , , and ) from the...
Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (, , , , and ) from the Great Barrier Reef (QLD, Australia) were thus collected, and their preliminary antioxidant and anti-inflammatory activities were evaluated. From the acetone extracts of five seagrass species subjected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging antioxidant assay, the extract of had the highest activity (half minimal concentration of inhibition (IC) = 138 µg/mL), with the aerial parts (IC = 119 µg/mL) possessing significantly higher antioxidant activity than the roots (IC ≥ 500 µg/mL). A human peripheral blood mononuclear cells (PBMCs) assay with bacterial lipopolysaccharide (LPS) activation and LEGENDplex cytokine analysis showed that the aerial extract of significantly reduced the levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 by 29%, 74%, and 90%, respectively, relative to the LPS treatment group. The aerial extract was thus fractionated with methanol (MeOH) and hexane fraction, and purification of the MeOH fraction by HPLC led to the isolation of 4-hydroxybenzoic acid (), luteolin (), and apigenin () as its major constituents. These compounds have been previously shown to reduce levels of TNF-α, IL-1β, and IL-6 and represent some of the major bioactive components of aerial parts. This investigation represents the first study of the antioxidant and anti-inflammatory properties of and the first isolation of small molecules from this species. These results highlight the potential for using seagrasses in treating inflammation and the need for further investigation.
PubMed: 38929693
DOI: 10.3390/life14060710