Strong Inhibitory Activity Research Articles

Exploring the physicochemical traits, antifungal capabilities, and 3D spatial complexity of hydroxyapatite with Ag+[sbnd]Mg2+ substitution in the biocomposite thin films

The silver/magnesium doped hydroxyapatite (AgMgHAp, Ca10−x-yAgxMgy(PO4)6(OH)2, xAg=0.05 and yMg=0.02) nanocomposites coatings were deposited on Si substrate using the dip coating technique. The resulting coatings were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FTIR-ATR) spectroscopy, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The EDS analysis highlighted the presence of the constitutive elements of the silver/magnesium doped hydroxyapatite (AgMgHAp) nanocomposites coatings. The surface microtexture of the AgMgHAp was assessed by atomic force microscopy (AFM) technique. The AFM data suggested the obtaining of a uniform deposited layer comprised of equally distributed nanoconglomerates. FT-IR studies highlighted the presence of vibrational modes associated with the phosphate and hydroxyl groups. No bands associated with silver or magnesium were observed. The XPS analysis highlighted the presence of the constituent elements of hydroxyapatite (Ca 2p, P 2 s, O 1 s), as well as dopants (Ag 3d, Mg 1 s and Mg 2p). The antifungal evaluation of AgMgHAp coatings was carried out using the Candida albicans ATCC 10231 fungal strain. The results of the antifungal assay revealed that the AgMgHAp coatings exhibited a strong inhibitory antifungal activity. Furthermore, the data highlighted that the AgMgHAp inhibited the development of biofilm on their surface. The results revealed that the antifungal activity of the coating varied based on the duration of incubation. On the other hand, the data also showed that AgMgHAp nanocomposites coatings inhibited the fungal cell adhesion and development from the early stages of the incubation. In addition to morphological analysis, we additionally take advantage of AFM images to investigate and explore the domain of fractal and multifractal analysis applied to the films under evaluation. Our studies indicates that nanocomposite coatings made from AgMgHAp demonstrate strong antifungal properties. Our studies indicates that nanocomposite coatings made from AgMgHAp demonstrate strong antifungal properties. These results suggest the potential of AgMgHAp nanocomposite coatings as a promising solution for developing innovative antifungal devices in biomedical applications.

Iloperidone and Temozolomide Synergistically Inhibit Growth, Migration and Enhance Apoptosis in Glioblastoma Cells.

Glioblastoma (GBM) is a fatal astrocytic glioma with poor prognosis and treatment resistance. Repurposing potential FDA-approved drugs like anti-psychotics can address the concerns in a timely and cost-effective manner. Epidemiological studies have shown that patients with schizophrenic using anti-psychotics have a low incidence of GBM. Therefore, we aimed to investigate the therapeutic potential of atypical anti-psychotic Iloperidone (ILO) alone and in combination with Temozolomide (TMZ) against GBM. The study assessed the growth inhibitory effect of ILO, TMZ, and their combination (ILO + TMZ) on U-87MG and T-98G cell lines using an MTT assay. The drug interaction coefficient (CDI) was determined, and doses with synergistic effects were used for subsequent experiments, including migratory, invasion, and TUNEL assays. The expressions of DRD2, β-catenin, Dvl2, Twist, and Slug were assessed by RTq-PCR, whereas the β-catenin protein expression was also determined by immunocytochemistry. ILO (p < 0.05) and TMZ (p < 0.01) significantly inhibited the growth of U-87MG cells at all tested doses. The combination of 60 µM of both drugs showed synergistic activity with CDI < 1. The inhibition of migration and apoptosis was more pronounced in the case of combination treatment (p < 0.001). Inhibition of the invading cells was also found to be significant in ILO- and combination-treated groups (p < 0.001). ILO and combination treatment also significantly downregulated the expression of DRD2, while TMZ upregulated the expression (p < 0.001). The expressions of β-catenin (p < 0.001), Dvl2 (p < 0.001), Twist (p < 0.001), and Slug (p < 0.001) were also significantly downregulated in all treatment groups as compared to the vehicle control. The data suggest that ILO possesses strong growth inhibitory activity, possibly due to its effect on DRD2 and β-catenin expression and has the potential to be repurposed against GBM.

Isolation and structure determination of a new bisabolane-type sesquiterpenoid with cytotoxicity from Penicillium oxalicum MZY-202312-521

Endophytic fungi can produce attractive secondary metabolites with various biological activities that have contributed significantly to pharmacotherapy. In this study, three bisabolane-type sesquiterpenoids, including a new one, namely, inonotic acid C (1), together with previously reported compounds (S)-(+)-11-dehydrosydonic acid (2) and sydonic acid (3), were isolated from a marine algal-derived endophytic fungus Penicillium oxalicum MZY-202312-521. Their structures were determined by means of extensive spectroscopic analyses. The absolute configurations of inonotic acid C (1) were established by single-crystal X-ray diffraction method. In vitro cytotoxic experiments on human A549, MCF-7, HeLa, and HepG2 carcinoma cell lines were carried out. The new compound inonotic acid C (1) was found to possess strong inhibitory activity against the MCF-7 cell line, with an IC50 value of 7.7 μM.

Anti-diabetic, anti-pancreatic lipase, and anti-protein glycation potential of Irvingia gabonensis stem bark extracts: in vitro and in silico studies.

Diabetes mellitus is a chronic metabolic disorder that affects glucose, lipid, and protein metabolism. Targeting these metabolic derangements can optimize the therapeutic strategies for this disease. Utilizing in vitro and in silico models, this study investigated the ability of aqueous and ethanol extracts of Irvingia gabonensis to inhibit α-amylase, α-glucosidase, pancreatic lipase, and protein glycation. High-performance liquid chromatography (HPLC) was used to identify the compounds found in the stem bark of I. gabonensis. In silico analysis determined the binding mode and mechanism of interactions between the enzymes and phytochemicals. With an IC50 value of 11.47µg/ml, the aqueous extract demonstrated higher inhibitory efficacy against α-amylase compared to the ethanol extract (IC50 19.88µg/ml). However, the ethanol extract had stronger inhibitory activities against α-glucosidase, pancreatic lipase, and protein glycation compared to the aqueous extract (IC50 values of 3.05, 32.85, 0.0014 versus 25.72, 332.42, 0.018µg/ml respectively). Quercetin ranked highest in binding energy with α-amylase (-6.6kcal/mol), α-glucosidase (-6.6kcal/mol), and pancreatic lipase (-5.6kcal/mol). This was followed by rhamnetin (6.5, 6.5, and 6.1kcal/mol respectively). Hydrogen bonding, hydrophobic interactions, and pi-pi stacking are forces responsible for the binding of quercetin and rhamnetin to these enzymes. Molecular dynamics simulation showed that the lead phytochemicals formed stable and energetically stabilized complexes with the target proteins. This study showed that the extracts of I. gabonensis stem bark had significant in vitro anti-diabetic, anti-pancreatic lipase, and anti-protein glycation activities. The strong binding affinities of some of the identified compounds could be responsible for the inhibitory potential of the extracts. I. gabonensis stem bark could be further explored as a natural remedy for the treatment of diabetes mellitus and its complications.

Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans.

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 μM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.

Novel quinazolin-2-yl 1,2,3-triazole hybrids as promising multi-target anticancer agents: Design, synthesis, and molecular docking study

In our study, a series of quinazoline-1,2,3-triazole hybrids (14a-r) have been designed and synthesized as multi-target EGFR, VEGFR-2, and Topo II inhibitors. All synthesized hybrids were assessed for their anticancer capacity. MTT assay revealed that compounds 14a, 14d, and 14k were the most potent hybrids against four cancer cell lines, HeLa, HePG-2, MCF-7, and HCT-116 at low micromolar range while exhibiting good selectivity against normal cell line WI-38. Sequentially, the three compounds were evaluated for EGFR, VEGFR-2, and Topo II inhibition. Compound 14d was moderate EGFR inhibitor (IC50 0.103 µM) compared to Erlotinib (IC50 0.049 µM), good VEGFR-2 inhibitor (IC50 0.069 µM) compared to Sorafenib (IC50 0.031 µM), and stronger Topo II inhibitor (IC50 19.74 µM) compared to Etoposide (IC50 34.19 µM) by about 1.7 folds. Compounds 14k and 14a represented strong inhibitory activity against Topo II with (IC50 31.02 µM and 56.3 µM) respectively, compared to Etoposide. Additionally, cell cycle analysis and apoptotic induction were performed. Compound 14d arrested the cell cycle on HeLa at G2/M phase by 17.53 % and enhanced apoptosis by 44.08 %. A molecular Docking study was implemented on the three hybrids and showed proper binding interaction with EGFR, VEGFR-2, and Topo II active sites.

Anti-atherogenic role of green tea (Camellia sinensis) in South Indian smokers

Ethnopharmacological relevanceGreen tea (Camellia sinensis) is a popular beverage consumed all over the world due to its health benefits. Many of these beneficial effects of green tea are attributed to polyphenols, particularly catechins. Aim of the studyThe present study focuses on underlying anti-platelet aggregation, anti-thrombotic, and anti-lipidemic molecular mechanisms of green tea in South Indian smokers. Materials and methods: We selected 120 South Indian male volunteers for this study to collect the blood and categorised them into four groups; control group individuals (Controls), smokers, healthy control individuals consuming green tea, and smokers consuming green tea. Smokers group subjects have been smoking an average 16–18 cigarettes per day for the last 7 years or more. The subjects (green tea consumed groups) consumed 100 mL of green tea each time, thrice a day for a one-year period. ResultsLC-MS analysis revealed the presence of multiple phytocompounds along with catechins in green tea extract. Increased plasma lipid peroxidation (LPO), protein carbonyls, cholesterol, triglycerides, and LDL-cholesterol with decreased HDL-cholesterol levels were observed in smokers compared to the control group and the consumption of green tea showed beneficial effect. Furthermore, docking studies revealed that natural compounds of green tea had high binding capacity with 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) when compared to their positive controls, whereas (−) epigallocatechin-3-gallate (EGCG) and (−) epicatechin-gallate (ECG) had high binding capacity with sterol regulatory element-binding transcription factor 1 (SREBP1c). Further, our ex vivo studies showed that green tea extract (GTE) significantly inhibited platelet aggregation and increased thrombolytic activity in a dose dependent manner. ConclusionIn conclusion, in smokers, catechins synergistically lowered oxidative stress, platelet aggregation and modified the aberrant lipid profile. Furthermore, molecular docking studies supported green tea catechins' antihyperlipidemic efficacy through strong inhibitory activity on HMG-CoA reductase and SREBP1c. The mitigating effects of green tea on cardiovascular disease risk factors in smokers that have been reported can be attributed majorly to catechins or to their synergistic effects.

MM/GB(PB)SA integrated with molecular docking and ADMET approach to inhibit the fat-mass-and-obesity-associated protein using bioactive compounds derived from food plants used in traditional Chinese medicine

IntroductionObesity is currently a major global concern, requiring the development of effective therapeutics. This study determines the inhibitory activity against FTO (fat mass and obesity-associated protein) of food plant-derived bioactive compounds of TCM (traditional Chinese medicine) importance, by in silico approaches. MethodsFood plant-derived phytochemicals, such as curcumin (CCMN), cajaisoflavone (CJIF), cyanidin-3-O-glucoside (C3OG) and pelargonidin-3-glucoside (P3GS), were selected as ligands, and docked to FTO. The reference FTO-inhibitor used was meclofenmic acid (MCFA). MDS (molecular dynamic simulations) was accomplished with 10 ns run for the docked complex of FTO with the most potential phytocompound. The phytochemicals were subjected to bioactivity scoring, Lipinski's rule of five screening, and ADMET prediction. Law ResultsMolecular docking demonstrated binding energies of -9.4, -8.8, -8.7 and -8.2 kcal/mol for CCMN, CJIF, C3OG and P3GS, respectively. The reference inhibitor MCFA had binding energy of -7.8 kcal/mol, and therefore, the FTO inhibition capacity of the ligands were in order of CCMN > C3OG > P3GS > CJIF > MCFA. The FTO residues His231, Ser229, Val228, Leu109, Tyr108 and Pro93 played crucial role in protein-ligands interaction displaying hydrogen bonds and hydrophobic contacts. MDS-based MM/GB(PB)SA binding free energies authenticated CCMN (-6.67/-8.77 kcal/mol) as a stronger FTO inhibitor than MCFA (0.19/-0.02 kcal/mol). Pharmacological properties of the phytochemicals predicted were comparable to MCFA standard. DiscussionTCM compounds of botanical origin are important for the effective management of obesity. In the current study, all the phytochemicals, the potential TCM ingredients, with acceptable pharmacological properties displayed excellent binding affinity and stronger inhibitory activity against FTO, compared to MCFA. FTO_CCMN displayed more energetic stability compared to FTO_MCFA using MM/GB(PB)SA approaches. Overall, this study paved the basis of FTO-associated obesity management with food plant-based therapeutics of TCM importance in the globe.

Inhibitory Activities of Five Fungicides on Alternaria suffruticosae and Their Field Control Efficacy Against Tree Peony Black Spot.

Tree peony black spot (TPBS), mainly caused by Alternaria suffruticosae, is a common leaf disease on the ornamental peony, which poses a great threat to the flower buds in the current year and the flowering quality in the next year. However, there is only one fungicide registered for the control of this disease, difenoconazole. In order to avoid the severe problem of pathogen resistance caused by long-term use of difenoconazole, it is necessary to screen more chemical fungicides for the prevention and control of TPBS. In this study, the biological activities of flutolanil, phenamacril, pyraclostrobin, and boscalid on mycelial growth, conidial germination, germ tube elongation, and sporulation quantity of A. suffruticosae were determined, and the field control efficacy was tested to evaluate the preventive and therapeutic activities. Difenoconazole was used as a control simultaneously. The results showed that pyraclostrobin had the strongest inhibitory effects on the conidial germination, mycelium growth, germ tube elongation, and sporulation quantity, with the average EC50 values of 0.0517, 0.5343, 0.0008, and 0.8068 μg/ml, respectively. The inhibitory activity of flutolanil on the four developmental stages of A. suffruticosae was weaker than that of the other three fungicides. Compared with flutolanil, boscalid, the other succinate dehydrogenase inhibitor, had more strong inhibitory effects on the mycelial growth and sporulation quantity, with the average EC50 values of 3.8603 and 1.4760 μg/ml, respectively. Phenamacril had a moderate inhibitory level and had more inhibitory activity on conidial germination and germ tube elongation, with the average EC50 values of 31.5349 and 5.2597 μg/ml, respectively. All of the four fungicides had no significant effects on the shape of spores and germ tubes. The control fungicide difenoconazole had the strongest inhibitory activity on mycelial growth, and the average EC50 value was only 0.3297 μg/ml. However, its inhibitory activity on the other three growth stages was not high. In the field trials, pyraclostrobin had high control efficacy on TPBS even at low concentrations, reaching a minimum of 62.6293%, which was higher than that of difenoconazole. The other three fungicides had higher control efficacy at high concentrations but decreased significantly at low concentrations. Considering the dosage and control efficacy, pyraclostrobin was the first choice for the control of TPBS. Pyraclostrobin is the preferred alternative fungicide to difenoconazole for the prevention and control of TPBS in production.

Thymol, a Monoterpenoid within Polymeric Iodophor Formulations and Their Antimicrobial Activities.

Antimicrobial resistance (AMR) poses an emanating threat to humanity's future. The effectiveness of commonly used antibiotics against microbial infections is declining at an alarming rate. As a result, morbidity and mortality rates are soaring, particularly among immunocompromised populations. Exploring alternative solutions, such as medicinal plants and iodine, shows promise in combating resistant pathogens. Such antimicrobials could effectively inhibit microbial proliferation through synergistic combinations. In our study, we prepared a formulation consisting of Aloe barbadensis Miller (AV), Thymol, iodine (I2), and polyvinylpyrrolidone (PVP). Various analytical methods including SEM/EDS, UV-vis, Raman, FTIR, and XRD were carried out to verify the purity, composition, and morphology of AV-PVP-Thymol-I2. We evaluated the inhibitory effects of this formulation against 10 selected reference strains using impregnated sterile discs, surgical sutures, gauze bandages, surgical face masks, and KN95 masks. The antimicrobial properties of AV-PVP-Thymol-I2 were assessed through disc diffusion methods against 10 reference strains in comparison with two common antibiotics. The 25-month-old formulation exhibited slightly lower inhibitory zones, indicating changes in the sustained-iodine-release reservoir. Our findings confirm AV-PVP-Thymol-I2 as a potent antifungal and antibacterial agent against the reference strains, demonstrating particularly strong inhibitory action on surgical sutures, cotton bandages, and face masks. These results enable the potential use of the formulation AV-PVP-Thymol-I2 as a promising antimicrobial agent against wound infections and as a spray-on contact-killing agent.

Antibacterial activity of lactic acid bacteria from black soldier fly (Hermetia illucens) larvae fed with empty fruit bunch and tofu waste

Antibiotic Growth Promoters (AGP) are prohibited for use in livestock due to their detrimental effects on consumer safety and livestock productivity. Probiotics are an alternative to AGP because they offer microorganisms that are beneficial to the livestock health. In this investigation, Lactic acid bacteria (LAB) from the Black Soldier Fly (BSF) larvae’s will be isolated, tested for their antimicrobial activities and molecularly identified using 16S rRNA gene with Polymerase Chain Reaction (PCR) technique. The larvae are fed with empty fruit bunch and tofu wastes as a source of prebiotics to the indigenous LAB. The LAB isolates were enumerated and morpho-biochemically characterized. Disk diffusion method was used to determine the antibacterial efficacy of LAB isolates against pathogenic bacteria, such as Salmonella enterica serotype Pullorum, Salmonella enterica serotype Typhimurium ATCC® 14028, and Escherichia coli ATCC® 8739. Nine bacterial isolates were purified from a population density of log 6 Colony-forming unit (CFU)/mL on de Man Rogosa Sharp (MRS) agar. Four LAB isolates were confirmed through (-) catalase activity and acids production (homofermentative). Two LAB isolates namely 5P3i3 and 5P3i5 were designated as the most potential strains against three pathogenic bacteria with the strongest inhibitory activities against E. coli, followed by S. enterica ser. Typhimurium and S. enterica ser. Pullorum. By using 16S rRNA gene sequencing, the two LAB isolates were assigned to Lactiplantibacillus pentosus and submitted to GenBank as L. pentosus strain 5P3i3 (OP445834.1) and L. pentosus strain 5P3i5 (OP445835.1). The results of this study will be further investigated with the characterization of potential isolates as probiotic candidates to be supplemented in poultry.

Active secondary metabolites from an endophytic fungus Fusarium solani MBM-5 of Datura arborea

This study investigated the chemical and biological activity of the secondary metabolites from an endophytic fungus Fusa-rium solani MBM-5 of Datura arborea. A total of six alkenoic acid compounds, including a new compound and five known ones, were isolated from the ethyl acetate extract of F. solani MBM-5 by using the chromatographic methods(open ODS column chromatography, silica gel column chromatography, Sephadex LH-20, and semi-preparative HPLC). The structures of the compounds were identified by using their physical and chemical data, spectroscopic methods(UV, IR, NMR, and HR-ESI-MS), and Mosher's reaction, which were fusaridioic acid E(1), fusaridioic acid C(2), fusaridioic acid A(3), L660282(4), hymeglusin(5), and hymeglnone(6). Compound 1 is new. MTT assay and Griss method were used to evaluate the growth inhibition of all the compounds against two tumor cells, as well as their influence and anti-inflammatory action on the release of NO from LPS-induced RAW264.7 cells. The results showed that compound 5 had strong growth inhibition activity against A549 and HepG2 cell lines, with IC_(50) values of 4.70 and 13.57 μmol·L~(-1), respectively. Compounds 1 and 6 significantly inhibited the release of NO from LPS-induced RAW264.7 cells, with IC_(50) values of 77.00 and 70.33 μmol·L~(-1), respectively.

Comparative effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide formation in potato chips

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.

Synthesis, biological evaluation, network pharmacology, and molecular docking of benzophenone as antitumor agents

Using Eaton's reagent or boron trifluoride ether, 24 compounds were synthesized in a 1- or 2-step reaction, with the conversion of the methoxy group to the hydroxyl group. Next, the in vitro antitumor activity of all compounds and the antioxidant activity of compounds 1 to 3 were investigated. Compounds 7, 13, 15, 17, 18, 20, 22, and 24 exhibited strong antitumor activity and were considered promising compounds. Among them, compounds 7, 13, and 18 exhibited very strong inhibitory activity against HL-60 cells with IC50 values of 0.55, 0.29, and 0.72 μM, respectively. Furthermore, compounds 1 to 3 exhibited moderate antioxidant activity and their mechanism of action was further validated by computational chemistry. Finally, the antitumor mechanism of the above 8 compounds was investigated through network pharmacology and molecular docking, and 19 key genes and 20 pathways were obtained. These results will allow future development of benzophenone and its derivatives.

Purification and characterization of betacyanin monomers from Hylocereus polyrhizus peel: A comparative study of their antioxidant and antidiabetic activities with mechanistic insights

Betacyanins have garnered escalating research interest for their promising bioactivities. However, substantial challenges in purification and separation have impeded a holistic comprehension of the distinct bioactivities of individual betacyanins and their underlying mechanisms. Herein, betanin and phyllocactin monomers with purity exceeding 95% were successfully obtained from Hylocereus polyrhizus peel using a feasible protocol. These monomers were subsequently employed for comparative bioactivity assessments to uncover underlying mechanisms and illuminate structure-activity relationships. Interestingly, phyllocactin exhibited superior antioxidant activities and 36.1% stronger inhibitory activity on α-glucosidase compared to betanin. Mechanistic studies have revealed that they function as mixed-type inhibitors of α-amylase and competitive inhibitors of α-glucosidase, with interactions predominantly driven by hydrogen bonding. Notably, phyllocactin demonstrated a greater binding affinity with enzymes than betanin, thereby substantiating its heightened inhibitory activity. Overall, our results highlight novel bioactivities of betacyanin monomers and provide profound insights into the intricate interplay between structures and properties.

Isolation and Identification of Chicken-Derived Lactic Acid Bacteria: In Vitro Probiotic Properties and Antagonistic Effects against Salmonella pullorum, Staphylococcus aureus, and Escherichia coli.

The development of probiotics capable of quickly colonizing the intestines of animals is important in promoting the healthy growth of livestock. The aim of this study was to screen lactic acid bacteria (LAB) from the intestinal microbiota of chickens with potential applications, and to evaluate their probiotic properties and antagonistic abilities against Salmonella pullorum, Staphylococcus aureus, and Escherichia coli. The results showed that a total of 79 strains with the characteristics of LAB were isolated from the chicken cecum microbiota, of which 7 strains exhibited strong inhibitory activity against S. pullorum, S. aureus, and E. coli. Performing 16s rDNA sequencing revealed that these seven strains were Lactiplantibacillus pentosus (n = 1), Lactiplantibacillus plantarum (n = 3), Lactiplantibacillus paraplantarum (n = 1), Lactiplantibacillus argentoratensis (n = 1), and Lactiplantibacillus fabifermentans (n = 1). Among them, L. pentosus R26 and L. plantarum R32 exhibited superior antibacterial activity. These two strains demonstrated high lactic acid production ability, with survival rates of 86.29% and 87.99% after 3 h of treatment at pH 1.5, 86.66% and 85.52% after 3 h of treatment with 0.5% bile salts, 90.03% and 88.16% after 2 h of treatment with simulated gastric fluid, and 98.92% and 98.22% after 2 h of treatment with simulated intestinal fluid, respectively. Co-cultivation with L. pentosus R26 for 24 h resulted in 50% of the pathogens being antagonized, while almost complete inhibition was observed following 72 h of co-cultivation. In conclusion, L. pentosus R26 and L. plantarum R32 exhibited high antibacterial activity and acid production capability, while also demonstrating satisfactory tolerance to low pH values and high concentrations of bile salts and digestive fluid. The probiotic characteristics and stress resistance of L. pentosus R26 were slightly superior to those of L. plantarum R32, indicating its potential for development as a probiotic.

Design, Synthesis and Evaluation of 8‐(Piperazin‐1‐yl) Imidazo[1,2‐a]Pyrazine Derivatives as Acetylcholinesterase Inhibitors and Antioxidants

AbstractA series of 8‐(piperazin‐1‐yl) imidazo [1,2‐a] pyrazine derivatives were designed and synthesized as acetylcholinesterase inhibitors (AChEIs) and antioxidants for the treatment of Alzheimer's disease (AD). Moreover, the biological evaluation results demonstrated that these synthesized compounds exhibited moderate inhibitory activities toward acetylcholinesterase (AChE) and radical scavenging activities. Among them, the compound with the strongest inhibitory activity against AChE had an IC50 value of 0.55 μM, which was higher than that of galantamine as the reference compound (IC50 value=5.01 μM). The compound with the strongest antioxidant activity had an IC50 value of 57.94 μM, which was lower than that of the ascorbic acid (IC50 value=25.70 μM) as the control drug. Furthermore, the results of molecular docking studies indicated that the compound could simultaneously bind to both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE, which was consistent with the mixed inhibition pattern shown by enzyme kinetic studies. The interaction's stability was also assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound in the cavity of the AChE. In addition, the molecular properties of all compounds were predicted online through the SwissADME, and most compounds matched the properties of most orally administered drugs. Based on the biological activity and molecular properties, 8‐(piperazin‐1‐yl) imidazo[1,2‐a] pyrazine derivatives as AChEI were valuable for further development.

Highly oxidized rearranged derivatives of quinochalcone C-glycosides from Carthamus tinctorius

Safflopentsides A−C (1−3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1−3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 μM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.

The Characteristics of Urease Enzyme of Green Bean Seeds (Vigna radiata L.) and Its Activity as An Antifungal Against Candida albicans

Urease is an enzyme responsible for catalyzing the hydrolysis reaction of urea into CO2 and NH3. The urease isolated in this study came from green bean seeds. The urease enzyme was then tested for its antifungal activity against Candida albicans. The research aims to extract and characterize the urease enzyme from green bean seeds and explore its potential use as an antifungal agent. Green bean seeds were smoothed with a mortar and pestle, followed by homogenization using a stirrer and cold centrifugation. The crude extract of the urease enzyme was assessed for its activity through the Nessler method and measured by employing a UV-Vis spectrophotometer at a wavelength of 500 nm. The well-diffusion method was conducted to determine the antifungal activity of rough enzyme extracts against C. albicans. Positive controls were 100% ketoconazole, and negative controls used a pH buffer of 7. The characterization of the urease enzyme from green bean seeds revealed the optimum urease activity at a concentration of 0.25 M, pH level of 7, and an incubation temperature of 35°C with a value of 32.115 U/mL. Maximum reaction rate (Vmax) and Michaelis-Menten constant value (KM) were obtained at 56.497 U/mL and 0.215 M, respectively. Antifungal tests of C. albicans resulted in strong inhibitory activity at a concentration of 100% crude urease extract of 12 mm inhibition zone. The inhibitory concentration value grows at least 0.5% by 0.25 mm and positive control of 19.802 mm.

Effect of WQ-3334 on Campylobacter jejuni carrying a DNA gyrase with dominant amino acid substitutions conferring quinolone resistance

IntroductionCampylobacteriosis stands as one of the most frequent bacterial gastroenteritis worldwide necessitating antibiotic treatment in severe cases and the rise of quinolones-resistant Campylobacter jejuni poses a significant challenge. The predominant mechanism of quinolones-resistance in this bacterium involves point mutations in the gyrA, resulting in amino acid substitution from threonine to isoleucine at 86th position, representing more than 90% of mutant DNA gyrase, and aspartic acid to asparagine at 90th position. WQ-3334, a novel quinolone, has demonstrated strong inhibitory activity against various bacteria. This study aims to investigate the effectiveness of WQ-3334, and its analogues, WQ-4064 and WQ-4065, with a unique modification in R1 against quinolones-resistant C. jejuni. MethodsThe structure-activity relationship of the examined drugs was investigated by measuring IC50 and their antimicrobial activities were accessed by MIC against C. jejuni strains. Additionally, in silico docking simulations were carried out using the crystal structure of the Escherichia coli DNA gyrase. ResultWQ-3334 exhibited the lowest IC50 against WT (0.188 ± 0.039 mg/L), T86I (11.0 ± 0.7 mg/L) and D90 N (1.60 ± 0.28 mg/L). Notably, DNA gyrases with T86I substitutions displayed the highest IC50 values among the examined WQ compounds. Moreover, WQ-3334 demonstrated the lowest MICs against wild-type and mutant strains. The docking simulations further confirmed the interactions between WQ-3334 and DNA gyrases. ConclusionWQ-3334 with 6-amino-3,5-difluoropyridine-2-yl at R1 severed as a remarkable candidate for the treatment of foodborne diseases caused by quinolones-resistant C. jejuni as shown by the high inhibitory activity against both wild-type and the predominant quinolones-resistant strains.