Strong Inhibitory Activity Research Articles

Optimization of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors, Leading to the Potent DS08701581.

Previously, we reported the new pyrido-pyridazinone template as a feline sarcoma-related (FER) tyrosine kinase inhibitor. Representative compound 1 (DS21360717) showed strong enzyme inhibitory activity (IC50 = 0.5 nM), however, its antitumor effect was insufficient, probably due to poor solubility and resultant low bioavailability (BA). In addition, the kinase selectivity was inadequate, which may result in certain safety risks. Here, we focused on derivatization of the unoptimized C-5 position to obtain promising FER inhibitors possessing strong antitumor effects and improved selectivity, referring to their X-ray crystal structure and the docking model with FES proto-oncogene tyrosine kinase as an FER surrogate. While establishing the synthetic route of the pyrido-pyridazinone scaffold, we obtained a desired compound via our derivatization. Our optimized compound 17c (DS08701581) showed the highest class cell-free and cell activities in this template, good oral BA, and improved kinase selectivity, resulting in significant tumor growth inhibition in the Ba/F3-FER tumor model without body weight loss.

A smooth vetch (Vicia villosa var.) strain endogenous to the broad-spectrum antagonist Bacillus siamensis JSZ06 alleviates banana wilt disease.

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense Tropical Race 4 (Foc TR4), poses a significant threat to banana production globally, thereby necessitating effective biocontrol methods to manage this devastating disease. This study investigates the potential of Bacillus siamensis strain JSZ06, isolated from smooth vetch, as a biocontrol agent against Foc TR4. To this end, we conducted a series of in vitro and in vivo experiments to evaluate the antifungal activity of strain JSZ06 and its crude extracts. Additionally, genomic analyses were performed to identify antibiotic synthesis genes, while metabolomic profiling was conducted to characterize bioactive compounds. The results demonstrated that strain JSZ06 exhibited strong inhibitory activity against Foc TR4, significantly reducing mycelial growth and spore germination. Moreover, scanning and transmission electron microscopy revealed substantial ultrastructural damage to Foc TR4 mycelia treated with JSZ06 extracts. Genomic analysis identified several antibiotic synthesis genes, and metabolomic profiling revealed numerous antifungal metabolites. Furthermore, in pot trials, the application of JSZ06 fermentation broth significantly enhanced banana plant growth and reduced disease severity, achieving biocontrol efficiencies of 76.71% and 79.25% for leaves and pseudostems, respectively. In conclusion, Bacillus siamensis JSZ06 is a promising biocontrol agent against Fusarium wilt in bananas, with its dual action of direct antifungal activity and plant growth promotion underscoring its potential for integrated disease management strategies.

Antimicrobial Assessment of Hand Sanitizers Formulated from Neem Leaf Extract (Azadirachta indica) and Coconut Shell Liquid Smoke

Abstract The widespread use of alcohol/ethanol-based hand sanitizers has raised concerns due to the concurrent issues of skin irritation, allergies, childhood poisoning risks, and the potential for bacterial resistance to antibiotics, which may disrupt the human digestive system. This study explores the potential of Neem leaves (Azadirachta indica) and liquid smoke as natural alternatives to alcohol-based antiseptics. The objective is to assess the antimicrobial efficacy of hand sanitizers containing Neem leaf extract and coconut shell liquid smoke against Escherichia coli and Salmonella typhimurium. Hand sanitizers were prepared by mixing 4g of Neem leaf extract with varying quantities of coconut shell liquid smoke (labeled as A1, A2, A3, A4, and A5, corresponding to 0g, 1g, 3g, 5g, and 7g, respectively). distilled water was then added until the total volume reached 100 ml. The solution was then stabilized with 0.5g of Carboxyl Methyl Cellulose (CMC) and 10g of glycerin. Results indicate that formulations A1, A2, A3, and A5 exhibit moderate inhibitory activity against Escherichia coli, with inhibition zone diameters of 6.02 mm, 8.17 mm, 9.67 mm, and 9.11 mm, respectively. Notably, formulation A4 displays strong inhibitory activity (11.15 mm). For Salmonella typhimurium, formulations A4 and A5 demonstrate very strong antimicrobial properties with inhibition zones measuring 11.68 mm and 12.59 mm, respectively. These findings suggest that hand sanitizers comprising Neem leaf extract and liquid smoke possess the potential as environmentally friendly, natural antiseptics.

Pichia pastoris Mediated Digestion of Water-Soluble Polysaccharides from Cress Seed Mucilage Produces Potent Antidiabetic Oligosaccharides.

Diabetes mellitus is a heterogeneous metabolic disorder that poses significant health and economic challenges across the globe. Polysaccharides, found abundantly in edible plants, hold promise for managing diabetes by reducing blood glucose levels (BGL) and insulin resistance. However, most of these polysaccharides cannot be digested or absorbed directly by the human body. Here we report the production of antidiabetic oligosaccharides from cress seed mucilage polysaccharides using yeast fermentation. The water-soluble polysaccharides extracted from cress seed mucilage were precipitated using 75% ethanol and fermented with Pichia pastoris for different time intervals. The digested saccharides were fractionated through gel permeation chromatography using a Bio Gel P-10 column. Structural analysis of the oligosaccharide fractions revealed the presence of galacturonic acid, rhamnose, glucuronic acid, glucose and arabinose. Oligosaccharide fractions exhibited the potential to inhibit α-amylase and α-glucosidase enzymes in a dose-dependent manner in vitro. The fraction DF73 exhibited strong inhibitory activity against α-amylase with IC50 values of 38.2 ± 1.12 µg/mL, compared to the positive control, acarbose, having an IC50 value of 29.18 ± 1.76 µg/mL. Similarly, DF72 and DF73 showed the highest inhibition of α-glucosidase, with IC50 values of 9.26 ± 2.68 and 50.47 ± 5.18 µg/mL, respectively. In in vivo assays in streptozotocin (STZ)-induced diabetic mice, these oligosaccharides significantly reduced BGL and improved lipid profiles compared to the reference drug metformin. Histopathological observations of mouse livers indicated the cytoprotective effects of these sugars. Taken together, our results suggest that oligosaccharides produced through microbial digestion of polysaccharides extracted from cress seed mucilage have the potential to reduce blood glucose levels, possibly through inhibition of carbohydrate-digesting enzymes and regulation of the various signaling pathways.

Heterologous expression of pediocin PA-1 in Pichia pastoris: cloning, expression, characterization, and application in pork bologna preservation.

Pediocin PA-1, an antimicrobial peptide derived from Pediococcus acidilactici PAC1.0, has a potential application as a food preservative thanks to its strong inhibitory activity against the foodborne pathogen L. monocytogenes. This study aimed to produce Pediocin PA-1 from the yeast P. pastoris and evaluate its characteristics. Gene encoding Pediocin PA-1 was integrated into P. pastoris X33 genome to establish the strain X33::ped, which could produce and secrete this peptide into culture medium. The antimicrobial activity of Pediocin PA-1 was examined using agar diffusion assay. The stability of pediocin PA-1 was determined based on its remaining antibacterial activity after exposure to proteases and extreme pH and temperatures. The potential use of this bacteriocin in food preservation was demonstrated using the L. monocytogenes infected pork bologna. The anticancer activity of Pediocin PA-1 was also investigated on some cancer cells using MTT assay. We established the yeast P. pastoris X33::ped capable of producing pediocin PA-1 with antimicrobial activity against L. monocytogenes and some other harmful bacteria. Pediocin PA-1 was stable at 100˚C and resistant against pH 1-12 for 1h, but susceptible to trypsin, α-chymotrypsin, and proteinase K. This peptide could reduce the number of L. monocytogenes in pork bologna by 3.59 log CFU/g after 7 days of storage at 4˚C. Finally, Pediocin PA-1 (25µg/ml) inhibited the proliferation of A549 and Hela cancer cells. We succeeded in producing active Pediocin PA-1 from P. pastoris and demonstrated its potential use in food preservation and pharmaceutical industry.

Phenolic content of Thai Bao mango peel and its in-vitro antioxidant, anti-cholinesterase, and antidiabetic activities

Plant phenolics have been known for various biological activities. This study aims to extract and examine the presence of phenolics in Bao mango (Mangifera indica L. var.) peel ethanolic extract (MPE). Further, antioxidant, anti-diabetic (α-amylase, and α-glucosidase inhibitory activity), and anti- Alzheimer’s disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) inhibitory activity) efficacy of MPE were determined. The results indicated that mangiferin (8755.89 mg/ 100 g extract) was the major phenolic compound in MPE. An antioxidant mechanism revealed that MPE had a higher radical scavenging ability (4266.70 µmol TE/g extract) compared to reducing power (FRAP) or oxygen radical absorption capacity (ORAC). Further in-vitro enzyme inhibitory assay against diabetic and AD involved enzymes showed that MPE had stronger inhibitory action against an enzyme involved in diabetes compared to their standard drug (Acarbose) (P < 0.05). While a lower IC50 value was observed against AD-involved enzymes compared to their standard drug (donepezil) (P < 0.05). The results show that Thai Bao mango peel byproduct can be a potential source of nutraceuticals to lower diabetes and improve cognitive health.

Designing and Synthesis of Novel Fexofenadine-Derived Hydrazone-Schiff Bases as Potential Urease Inhibitors: In-Vitro, Molecular Docking and DFT Investigations.

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC50=10.19±0.16 μM), 11 (IC50=15.05±1.11 μM), 10 (IC50=17.01±1.23 μM), 9 (IC50=17.22±0.81 μM), 13 (IC50=19.31±0.18 μM), and 14 (IC50=19.62±0.21 μM) displayed strong inhibitory action better than the standard thiourea (IC50=21.14±0.24 μM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies.

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.