Synthetic Compounds Research Articles

Anti-bacteria, anti-biofilm, and anti-virulence activity of the synthetic compound MTEBT-3 against carbapenem-resistant Klebsiella pneumoniae strains ST3984

PurposeThe rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) has led to increased morbidity and mortality in clinical patients, highlighting the urgent need for effective antibacterial agents. MethodsWe obtained a synthetic compound, MTEBT-3, using hydrophobic triphenylamine as the skeleton and hydrophilic ammonium salts. We determined the MIC of MTEBT-3 using the macro-broth susceptibility testing method. We isolated a clinical CRKP strain ST3984 and performed synergistic antibiotic sensitivity tests, time-kill assays, and resistance evolution studies. Biofilm formation under sub-MIC conditions was evaluated using crystal violet staining and CLSM. Additionally, biofilm proteins and polysaccharides were quantified. We assessed the bactericidal mechanism of MTEBT-3 by examining the integrity of CRKP bacterial cell membranes and analyzing the transcription of virulence-regulating genes via quantitative real-time PCR. ResultsMTEBT-3 exhibited broad-spectrum antibacterial activity with a low resistance rate, achieving the MIC of 8 μg/mL. The compound displayed additive effects with meropenem and imipenem and synergistic effects with tigecycline. It maintained its efficacy over multiple bacterial generations, with no significant increase in resistance observed. Under sub-MIC conditions, the biomass of biofilms was significantly reduced, and the levels of proteins and polysaccharides within the biofilms were markedly lowered in a concentration-dependent manner. The bactericidal mechanism of MTEBT-3 involved disrupting the integrity of CRKP bacterial cell membranes, leading to increased permeability. Quantitative real-time PCR results showed that MTEBT-3 effectively suppressed the expression of key virulence genes, including fimH, wbbM, rmpA, and rmpA2, which are associated with biofilm formation and bacterial adhesion. ConclusionThe significant antimicrobial activity of MTEBT-3 against clinically isolated CRKP, along with its synergistic or additive effects with commonly used antibiotics, positions it as a promising candidate for treatment. Its ability to disrupt biofilm formation and reduce virulence factor expression further underscores its potential in managing CRKP infections.

Schiff Bases: A Captivating Scaffold with Potential Anticonvulsant Activity.

One of the most important organic compounds, also known as a Schiff base, imine, or azomethine, has been associated with several biological processes. The group is a component of both natural or synthetic chemicals and functions as both a precursor and an intermediary in the synthesis of therapeutically active substances. The review highlights the various non-metal Schiff bases' structure-activity relationship (SAR) studies, general model, docking, and design approach for anticonvulsant actions. Schiff bases serve as linkers in numerous synthetic compounds with a variety of activities, according to the findings of several investigations. As a result, the current review will give readers a thorough understanding of the key ideas put forth by different researchers regarding the anticonvulsant properties of Schiff bases. It will serve as a valuable information source for those planning to synthesize new anticonvulsant molecules that contain Schiff bases as pharmacophores or biologically active moieties.

The nephroprotective potential of selected synthetic compound against gentamicin induced nephrotoxicity

BackgroundNephrotoxicity, the rapid impairment of kidney function caused by harmful drugs and chemicals, affects about 20% of cases and is projected to become a leading cause of death by reactive oxygen species (ROS). Gentamicin (GM), an aminoglycoside antibiotic is one of the well know drugs/chemicals to cause nephrotoxicity both in humans and animals.MethodsA study on the effects of a synthetic phenolic compound, called 5-a, on GM-induced nephrotoxicity in male Wistar albino rats was conducted. The rats were grouped into five groups: normal control (NC), GM control (GM), positive control (GM + Dexa), treatment I (GM + 5-a 5 mg/kg) and treatment II (GM + 5-a 10 mg/kg). Throughout the experiment, the rats’ weights were monitored, and at its conclusion, their serum and kidney tissues were analyzed for renal function indicators and inflammatory markers. The study also included histopathological evaluations, molecular docking studies, blood and urine analyses for electrolyte changes, and behavioural assessments for central nervous system impact.Results2-{5-[(2-hydroxyethyl)-sulfanyl]-1,3,4-oxadiazol-2-yl} phenol (5-a) significantly protected against renal damage by reducing inflammatory markers, improving antioxidant defences, and decreasing kidney injury, particularly at higher doses. The findings suggest that compound 5-a, due to its anti-inflammatory and antioxidant properties, could be a promising therapeutic option for reducing gentamicin-induced nephrotoxicity and potentially for other kidney disorders in the future.ConclusionThese findings highlight the therapeutic effects of compound 5-a in alleviating gentamicin-induced nephrotoxicity.

Novel triazole-nucleoside hybrids as potential antimicrobial agents: Design, synthesis, and molecular docking

Despite decoding many important genes in the formation of microbes, particularly pathogenic and mutant ones that lead to resistance to a wide range of antibiotics, this opens the door to discovering new antimicrobial compounds, whether synthetic or natural in origin. A new set of nucleoside-triazole hybrids was created to provide a more effective topoisomerase II for microbial therapy. All freshly synthesized compounds' structures were confirmed using spectral data and elemental analysis. The newly synthesized compounds were docked to the area of topoisomerase II's active site; compounds 3, 7, 15, 18, and 19 exhibited distinct hydrogen bonding formation and pi-pi interactions. The results of testing every compound against six different microbial strains were expressed as the width of the inhibitory zone.Except for Aspergillus Niger, most of the synthetic compounds inhibit all bacteria. Compounds 15 and 19 had the lowest MIC values (1.95, 3.9 µg/mL against B. subtills and 1.95, 3.9 µg/mL against S. aureus). Nucleoside 15 had MBC values between 3.9 and B. subtills. The in-vitro topoisomerase II enzyme assay revealed that compounds 3, 15, 18, and 19 had IC50 values of 0.17, 0.05, 0.13, and 0.08 µmol/mL, respectively. A transmission electron microscope (TEM) was utilized to assess morphological changes on the bacterial surface following treatment with nucleoside 15. It was discovered that nucleoside 15 induced substantial cell wall weakening, which exacerbated cell membrane rupture.

Immunostimulant In Fish Hatchery- A Tool In Pharmacological Research

Fish is an aquatic animal that is used as food and presently they are used in scientific research. They provide a simple system for biomedical research and hence there is an increase in demand for fish production due to its dynamic purposes. The fish are less sentient and they have a high potency with the homology of mammals hence they are used as a model in pharmacological research. The various fish that are used are zebra fish, rainbow trout fish, medaka fish, etc. Various husbandry techniques were introduced to increase the production of fish. Their intensification led to poor-quality of fish production. Immunostimulants are drugs that enhance the innate immunity of fish and increase their resistance to the disease. They are biological and synthetic compounds that increase phagocytic, lysosomal, and bactericidal activity by directly activating the immune cells and NK cells and helping in the control of disease. They are used in the pharmacological research of toxicology, genetics, cancer research, biomedicine, neurobiology, endocrinology, ecology, and gerontology, and also in the development of biology and act as a model to provide elemental knowledge on biological science.

Semisynthesis, Structure Elucidation and Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactones with Interesting Ketal Groups.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti-M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5' and C-6', exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5' and C-6' on this compound's activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5' and C-6'. The R/S configuration of the diastereoisomer at C-13' was further determined through an NOE correlation analysis of CH3 or CH2 at the derivative C-13' position and the H-5' and H-6' by means of a 1D NOE experiment. Further comparative 1H NMR analysis of diastereoisomers showed the difference in the chemical shift (δ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15-24 and 28-35 demonstrated promising activity against M. marinum, with MIC90 values ranging from 70 to 90 μM, closely approaching the MIC90 of isoniazid. The preliminary structure-activity relationships showed that the ketal groups with aromatic rings at C-5' and C-6' could enhance the inhibition of M. marinum. Further study demonstrated that compounds 23, 24, 29, and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Stable Efficient Solid-State Supercapacitors and Dye-Sensitized Solar Cells Using Ionic Liquid-Doped Solid Biopolymer Electrolyte.

As synthetic and nonbiodegradable compounds are becoming a great challenge for the environment, developing polymer electrolytes using naturally occurring biodegradable polymers has drawn considerable research interest to replace traditional aqueous electrolytes and synthetic polymer-based polymer electrolytes. This study shows the development of a highly conducting ionic liquid (1-hexyl-3-methylimidazolium iodide)-doped corn starch-based polymer electrolyte. A simple solution cast method is used to prepare biopolymer-based polymer electrolytes and characterized using different electrical, structural, and photoelectrochemical studies. Prepared polymer electrolytes are optimized based on ionic conductivity, which shows an ionic conductivity as high as 1.90 × 10-3 S/cm. Fourier transform infrared spectroscopy (FTIR) confirms the complexation and composite nature, while X-ray diffraction (XRD) and polarized optical microscopy (POM) affirm the reduction of crystallinity in biopolymer electrolytes after doping with ionic liquid (IL). Thermal and photoelectrochemical studies further affirm that synthesized material is well stable above 200 °C and shows a wide electrochemical window of 3.91 V. The ionic transference number measurement (t ion) confirms the predominance of ionic charge carriers in the present system. An electric double-layer capacitor (EDLC) and a dye-sensitized solar cell (DSSC) were fabricated by using the highest conducting corn starch polymer electrolyte. The fabricated EDLC and DSSC delivered an average specific capacitance of 130 F/g and an efficiency of 1.73% in one sun condition, respectively.

Optimization of Bangladesh and Malaysian genotype recombinant reporter Nipah viruses for in vitro antiviral screening and in vivo disease modeling

Nipah virus (NiV) causes near-annual outbreaks of fatal encephalitis and respiratory disease in South Asia with a high mortality rate (∼70%). Since there are no approved therapeutics for NiV disease in humans, the WHO has designated NiV and henipaviral diseases priority pathogens for research and development. We generated a new recombinant green fluorescent reporter NiV of the circulating Bangladesh genotype (rNiV-B-ZsG) and optimized it alongside our previously generated Malaysian genotype reporter counterpart (rNiV-M-ZsG) for antiviral screening in primary-like human respiratory cell types. Validating our platform for rNiV-B-ZsG with a synthetic compound library directed against viral RNA-dependent RNA polymerases, we identified a hit compound and confirmed its sub-micromolar activity against wild-type NiV, green fluorescent reporter, and the newly constructed bioluminescent red fluorescent double reporter (rNiV-B-BREP) NiV. We furthermore demonstrated that rNiV-B-ZsG and rNiV-B-BREP viruses showed pathogenicity comparable to wild-type NiV-B in the Syrian golden hamster model of disease, supporting additional use of these tools for both pathogenesis and advanced pre-clinical studies in vivo.

Efficacy of Pogostemon cablin essential oil loaded chitosan nanoemulsion as novel coating agent for inhibition of potato sprouting and maintenance of storage quality

Application of synthetic compounds to inhibit potato sprouting is a major challenge in the storage conditions. The replacement of synthetic compounds by essential oils for inhibition of potato sprouting is of current research hotspot. This is the first time investigation on encapsulation of Pogostemon cablin essential oil into chitosan nanoemulsion (Ne-PCEO) and its application as coating agent for anti-sprouting activity of potato tubers. The Ne-PCEO was characterized through SEM, DLS, FTIR, and XRD assay along with controlled delivery of PCEO. The Ne-PCEO coating inhibited in-vivo potato sprouting and regulated gibberellins (GA3) and aminocyclopropane-1-carboxylate (ACC) content along with impediment of respiration rate over 90 days of storage at 25 ± 2 °C (RH ∼ 70 %). The Ne-PCEO coating also prevented the weight loss, starch degradation, and increased the reducing sugar content of tubers without affecting the sensory qualities (p < 0.05), which strongly recommends its potential application as novel anti-sprouting coating agent for maintenance of potato storage quality.

Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches

Abstract The current study attempted to synthesize methoxy-substituted Schiff’s bases, namely MK1 and MK2, and evaluate their antidiabetic effects using in vitro, in vivo, and molecular docking studies. Experimental animals (rat model) received the synthetic compounds, MK1 and MK2, orally in doses of 25 and 50 mg/kg body weight, respectively. When comparing compound MK2 at the tested doses to glibenclamide on day 28, the diabetic rats’ blood glucose levels were nearly normal (139.02 and 121.23 mg/dL at 25 and 50 mg/kg body weight doses). The IC50 for MK1 against α-glucosidase inhibitory potential was found to be 281.29 μg/mL, while for MK2, it is reported to be 204.69 μg/mL. Furthermore, the acute toxicity, lipid profile, and its effect on blood biochemical parameters were also examined. In addition, through in silico analysis, the binding of MK1 and MK2 was elucidated with α-glucosidase enzyme, showcasing its antidiabetic mechanism at molecular levels. The in silico studies also predicted the two compounds to be inactive toward the human hERGs cardiac potassium channel, which indicates no potential risk of cardiac toxicity. Overall, the toxicity predictions suggest that compounds MK1 and MK2 are non-toxic and non-carcinogenic.

Determination of selenium in polyheteroatomic organic compounds by microwave plasma atomic emission spectrometry

Currently, the problem of selenium determination in various objects attracts a large number of scientists. Interest in this area is attributed to the biological importance of selenium, since it is both an important nutrient and has a toxic effect on the body, depending on its amount and the properties of the compounds in which it is contained. Checking the purity of selenium-containing organic compounds (both determination of impurities and analysis of the basic composition), which is carried out by methods of elemental analysis, is an important task, however, in modern literature there is lack of information regarding this problem. The purpose of the presented study is to develop a method for the determination of selenium in the basic composition of synthetic polyheteroatomic organic compounds by microwave plasma atomic emission spectrometry. Various selenodiazole derivatives were mainly used for analysis. Optimal conditions for sample preparation and atomic emission determination of the selenium content were specified. To mineralize the substances under study, oxygen flask combustion was used with the addition of potassium nitrate, which improves combustion and prevents the formation of soot. Hydrochloric acid at a concentration of 0.1 M was used as an absorption solution. It is noted that before measurements it is necessary to purge the monochromator and optimize the pressure in the atomic emission spectrometer nebulizer and optimize pressure in the atomizer. In addition, the number of replicates and sampling time were increased to optimize selenium measurement. Under specified conditions, the metrological characteristics of the technique were determined: the detection limit and quantitation limit, intra-laboratory precision and accuracy. Selenium was determined in 11 synthetic organic compounds with selenium content ranged from 12 to 51%. The error of the analysis did not exceed 0.3%, which meets the requirements of organic elemental analysis.

Synthesis, antibacterial, anti-urease, DFT and molecular docking studies of novel bis-1,3,4-thiadiazoles

A series of 2-substitutedamino-1,3,4-thiadiazoles (4a-4j) were synthesized starting from various isothiocyanate derivatives. The newly synthesized compounds were characterized by 1H NMR, 13C NMR, and elemental analysis. All compounds were tested for antibacterial activity against Proteus vulgaris (ATCC 7829) via the microbroth dilution technique. Among them, compound 4h emerged as the most potent antibacterial agent with MIC value of 4.1 μM. All synthetic compounds were additionally evaluated for their urease inhibitory activity and exhibited good inhibitory potential against urease with IC50 values in the range of 1.732 ± 0.186 - 3.786 ± 0.300 μM as compared to the standard thiourea (IC50 = 11.008 ± 0.932 μM). Compounds 4d, 4h and 4i showed significant inhibitory effects with IC50 values of 1.981 ± 0.265, 1.732 ± 0.186 and 1.937 ± 0.173 μM, respectively. In silico molecular docking study showed the critical interactions of compound 4h with the active site of the urease. According to DFT, compounds 4j and 4d (with low ΔE=4.536 eV and 4.629 eV values, respectively) are more chemically reactive than the other molecules, in which consistent with their inhibitory potentials against the urease enzyme. Molecular Dynamics simulations also were performed to assess the energetic features of the urease in complex with compound 4h. Furthermore, the predicted ADMET characteristics of the compound 4h was calculated using QikProp to gain insights into its pharmacokinetic properties. These newly identified inhibitors of the urease enzyme can serve as leads for further antibacterial drug research and development.

Thyroid under Attack: The Adverse Impact of Plasticizers, Pesticides, and PFASs on Thyroid Function

Endocrine-disrupting chemicals (EDCs) are synthetic or natural compounds that interfere with the endocrine system, inducing harmful effects on organisms depending on the dose and period of exposure. Numerous studies have identified concerning amounts of EDCs in environmental and human samples. The thyroid gland is essential for thyroid hormone production and controls several body functions. Several EDCs have been classified as thyroid disruptors, impairing thyroid hormone production, synthesis, metabolism, transport, and/or actions. Notably, thyroid disorders are the second most prevalent endocrine disease worldwide, with incidence increasing significantly in recent years. Some studies have correlated this rise in thyroid dysfunctions and cancers with increased exposure to EDCs. Although many EDCs are linked to thyroid dysfunction, this review focuses on the deleterious effects of plasticizers, organochlorine pesticides, and per- and poly-fluoroalkyl substances on thyroid function. These contaminants are commonly found in food, water, and everyday products. Although the impact of human exposure to these EDCs is controversial, numerous epidemiological, in vivo, and in vitro studies have indicated their harmful effects on thyroid function. Given the critical role of thyroid function and hormone production in growth, metabolism, and development, this review summarizes the consequences of exposure to thyroid disruptors for human health.

Eco‐friendly approaches for synthesis of indolyl 1H‐pyrroles using rice‐husk‐derived carbonaceous sulfonation as the green catalyst

AbstractBACKGROUNDAmorphous carbon‐bearing sulfonic acid groups (AC–SO3H) are a kind of solid acid that exhibits high acidity and belongs to the new generation of solid acids. The presence of acidic functional groups, including carboxylic acid, phenolic and sulfonic acid groups, allows for several key activities such as strong Brønsted acid properties, high surface area, stability, reusability and recyclability.RESULTSIn this work, we synthesized indolyl 1H‐pyrroles from indoles, phenylglyoxal monohydrate, 1,3‐diketones and ammonium acetate using rice‐husk‐derived carbonaceous sulfonation (AC–SO3H) as a catalyst. We explored the impact of catalyst quantity, reaction time, solvent, mineral acid and temperature in order to determine the optimal reaction conditions. Additionally, indolyl 1H‐pyrrole derivatives were also synthesized based on the optimal conditions that were completely investigated, and the structure of these synthetic compounds was characterized by 1H‐ and 13C‐nuclear magnetic resonance.CONCLUSIONThe yield of indolyl 1H‐pyrroles was up to 84% in 6 h at 100 °C with the activity of 30 mg AC–SO3H. Besides, based on the optimal conditions, 21 indolyl 1H‐pyrrole derivatives were formed with the high‐yield and green method. The catalyst could be reused multiple times without a significant decrease in catalytic performance. According to the findings from the experiments, a potential mechanism that included a radical process has been suggested. This eco‐friendly approach provided a straightforward and efficient method to produce a variety of indole–pyrrole conjugates in a single step. © 2024 Society of Chemical Industry (SCI).

Development and validation of a novel HPLC-MS/MS method for the quantitative determination of PFASs in non-hazardous solid waste samples

Perfluoroalkyl substances (PFASs) are a heterogeneous group of fluorinated synthetic compounds characterised by the presence of a hydrophobic carbonyl chain at different fluorination rates and by a terminal hydrophilic group. Because of their persistence and mobility, PFASs have been widely detected in ecosystems and living organisms, leading to their classification as persistent organic pollutants (POPs). Hence, monitoring the PFASs content in solid waste meant for disposal in non-hazardous landfills can be crucial, since leachate can pose a significant pollution threat to farmlands and aquifers.Therefore, a QuEChERS and SPE pretreatment with HPLC-MS/MS detection method for 10 different PFASs in solid waste samples was developed in this study. Different sample preparation approaches have been evaluated, taking into account the lack in the literature of this complex matrix.An innovative application using the Captiva EMR cartridge for the clean up (designed to be applied to lipidic matrix) was proposed and a multiresidual HPLC-MS/MS method for the analysis of PFASs in internal waters was extended to the investigation of non-lipidic samples as solid wastes. The method was then validated through 6 blanks and 6 spiked samples, according to the UNI EN ISO/IEC 17025. The optimized method showed satisfactory performance with recoveries ranging from 89.8 % to 106.5 % and with LOD and LOQ ranging between 0.0023 – 0.09 µg/L and 0.006 – 0.13 µg/L, respectively, for each of the PFASs under consideration. In addition, this approach demonstrated to be reliable and time consuming due to its capability for determining PFASs in waters and in solid wastes simultaneously in a single chromatographic run.

Exploring the anticancer properties of indole pyrimidine derivatives: Synthesis, structural insights, docking analysis, and in vitro evaluation

The nitrogen containing heterocyclic and chalcones moiety widely recognized as favorable combination of diagnostic and therapeutic facilities in medicinal chemistry. In particular, indole analogs play a very important medicinal role in pharmacology activities, hence, drugs like pindolol, indomethacin, oxypertine, ellipticine, arbidol and ate viridine are well known in market. In this view, the title compounds 4(a-j) were synthesized in good yield. The purified compounds were explained by spectroscopic procedures (FT-IR, 1H NMR, 13CNMR, and LC-MS), and lastly, all synthetic compounds have in-vitro efficacy assessed against the HeLa human cervical cancer and MCF-7 human breast cancer cell lines, and their efficacy was compared to that of the well-known anticancer drug methotrexate (Methotrexate). Compounds 4a, 4b, 4c, and 4e from the series (4a-j) demonstrated the most notable inhibitory activity. The cytotoxicity evaluation of these newly synthesized compounds revealed that 4a, 4b, 4c, and 4e were the most toxic to HeLa cells, with IC50 values for growth inhibition of 20.41 ± 3.14, 23.54 ± 3.27, 24.77 ± 2.14, and 26.10 ± 1.58, respectively. These compounds exhibited an even stronger growth-inhibitory effect on MCF-7 cells, with IC50 values of 18.84 ± 2.69, 19.45 ± 3.14, 22.83 ± 2.68, and 21.80 ± 1.68, respectively. In comparison, methotrexate (Methotrexate) showed IC50 values of 28.29 ± 1.0 for HeLa cells and 45.08 ± 2.61 for MCF-7 cells. Additionally, compounds 4a, 4b, 4c, and 4e played a crucial role in interacting with the catalytic domain of PDE3, demonstrating IC50 values for PDE3A inhibition of 8.05 ± 1.27, 7.55 ± 2.14, 15.09 ± 1.54, and 17.12 ± 3.14, respectively. These results are compared with Cilostazol, a known PDE inhibitor, which exhibited an IC50 of 0.00368 ± 3.14. In-silico studies revealed that compounds (4a, 4b, and 4c) are comparatively very efficient in binding with PDE3A which was further validated with MMGBSA and MDSs.

Design, synthesis, and biological evaluation of tetrahydropyrimidine analogue as GSK-3β/Aβ aggregation inhibitor and anti-Alzheimer’s agent

The complex nature of Alzheimer’s disease (AD) etiopathology is among the principal hurdles to developing effective anti-Alzheimer agents. Tau pathology and Amyloid-β (Aβ) accumulation are hallmarks and validated therapeutic strategies of AD. GSK-3β is a serine/threonine kinase involved in tau phosphorylation. Its excessive activity also contributes to the production of Aβ plaques, making GSK-3β an attractive AD target. Taking this into account, In this article, we outline the design, synthesis, and biological validation of a focused library of 1,2,3,4-tetrahydropyrimidine based derivatives as inhibitors of GSK-3β, tau phosphorylation, and Aβ accumulation. The inhibitory activity of forty nine synthetic compounds was tested against GSK-3β and other AD-relevant kinases. The kinetic experiments revealed the mode of GSK-3β inhibition by the most potent compound 44. The in- vitro drug metabolism and pharmacokinetic studies were thereafter performed. The anti-aggregation activity of the most potent GSK-3β inhibitor was tested using AD transgenic Caenorhabditis elegans (C. elegans) strain CL2006 for quantification of Aβ plaques and BR5706 C. elegans strain for tau pathology evaluation. We then evaluated the blood–brain barrier permeability and got promising results. Therefore, we present compound 44 as a potential ATP-competitive GSK-3β inhibitor with good metabolism and pharmacokinetic profile, anti-aggregation properties for amyloid beta protein, and reduction in tau-phosphorylation levels. We recommend more investigation into compound 44-based small molecules as possible targets for AD disease-modifying treatments.

Perfluorodecanoic acid induces the increase of innate cells in zebrafish embryos by upregulating oxidative stress levels

Several studies reported that the widespread use of perfluoroalkyl and polyfluoroalkyl substances (PFASs) causes increased environmental pollution, subsequently impacting aquatic organisms. Perfluoroalkyl substances such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) reportedly cause cardiotoxicity, neurotoxicity, and developmental toxicity in different organisms. However, whether perfluorodecanoic acid (PFDA), a widely used perfluoroalkyl substance, induces animal embryos developmental toxicity remain unknown. Here, we explored the immunotoxicity and associated mechanisms of PFDA in zebrafish embryos via RNA sequencing, morphological assessment and behavioral alteration detection following exposure to 0.5, 1 and 2 mg/L of PFDA. Interestingly, We found that with the increase of PFDA to drug concentration, including neutrophils and macrophages, significantly increased the number of inherent cells, immune related genes expression. Furthermore, oxidative stress increased in the PFDA-treated embryos in a dose-dependent manner and inhibition of oxidative stress levels effectively rescued the number of neutrophils. Changes in embryonic behavior were observed after exposure to PFDA. Overall, our results suggest that PFDA may induce innate immune response by accumulation of oxidative stress in zebrafish at early developmental stages, and concern is needed about its environmental exposure risks for animals embryos development. Environmental implicationPerfluorinated and polyfluorinated alkyl substances (PFASs) are a class of synthetic organic compounds containing fluorine widely used as lubricants, surfactants, insecticides, etc. The PFDA, a typical perfluorinated compound, is often used as a wetting agent and flame retardant in industries.Several studies showed that PFASs can cause serious environmental pollution, leading to developmental toxicity to various animals, including reproductive toxicity, liver toxicity, heart toxicity, neurotoxicity, and immunotoxicity.However, there are still limited studies on the effects and mechanisms of PFDA on aquatic organisms. Therefore, there is a need to evaluate the ecological risks of PFDA in animals.

Matrix Metalloproteinases on Skin Photoaging.

Skin aging is characterized by an imbalance between the generation and degradation of extracellular matrix molecules (ECM). Matrix metalloproteinases (MMPs) are the primary enzymes responsible for ECM breakdown. Intrinsic and extrinsic stimuli can induce different MMPs. However, there is limited literature especially on the summary of skin MMPs and potential inhibitors. We aim to focus on the upregulation of MMP expression or activity in skin cells following exposure to UV radiation. We also would like to offer valuable insights into potential clinical applications of MMP inhibitors for mitigating skin aging. This article presents the summary of prior research, which involved an extensive literature search across diverse academic databases including Web of Science and PubMed. Our findings offer a comprehensive insight into the effects of MMPs on skin aging after UV irradiation, including their substrate preferences and distinct roles in this process. Additionally, a comprehensive list of natural plant and animal extracts, proteins, polypeptides, amino acids, as well as natural and synthetic compounds that serve as inhibitors for MMPs is compiled. Skin aging is a complex process influenced by environmental factors and MMPs. Research focuses on UV-induced skin damage and the formation of Advanced Glycosylation End Products (AGEs), leading to wrinkles and impaired functionality. Inhibiting MMPs is crucial for maintaining youthful skin. Natural sources of MMP inhibitor substances, such as extracts from plants and animals, offer a safer approach to obtain inhibitors through dietary supplements. Studying isolated active ingredients can contribute to developing targeted MMP inhibitors.

Molecular docking, microwave-assisted synthesis, characterization, and preliminary evaluation of the anti-microbial activity of new sulfonamide derivatives of the 1, 2, 4-triazole-3-thiol ring system

A new sulfonamide derivative containing a 1,2,4-Triazole-3-thiol ring was synthesized and characterized using FT-IR and 1H-NMR. The microwave-assisted chemical synthesis of the 1,2,4-Triazole-3-thiol ring system resulted in good yield and purity. The synthetic compounds were then subjected to in vitro evaluation for antimicrobial study. All synthetic compounds show high activity against Gram-positive bacteria (S. aureus, S. pneumonia, and B. subtilis) and high activity against Gram-negative bacteria (P. aeruginosa, and H. pylori), with less activity against (N. gonorrhoeae, and E. coli). Also, it shows high activity against fungi (C. albicans). In this study, we utilized computational methods to design new derivatives that target the carbonic anhydrase enzyme of H. pylori (PDB: 4YGF). All the target compounds interact with the enzyme’s active site, resulting in a disturbance of the acid-base balance affecting the virulence and pathogenicity.