Μg mL-1 Research Articles

Antifungal profile against Candida auris clinical isolates of tyroscherin and its new analog produced by the deep-sea-derived fungal strain Scedosporium apiospermum FKJ-0499.

A new antifungal compound, named N-demethyltyroscherin (1), was discovered from the static fungal cultured material of Scedosporium apiospermum FKJ-0499 isolated from a deep-sea sediment sample together with a known compound, tyroscherin (2). The structure of 1 was elucidated as a new analog of 2 by MS and NMR analyses. The absolute configuration of 1 was determined by chemical derivatization. Both compounds showed potent in vitro antifungal activity against clinically isolated Candida auris strains, with MIC values ranging from 0.0625 to 4 µg ml-1.

Green Synthesis of Novel Silver Nanoparticles Using Salvia blepharophylla and Salvia greggii: Antioxidant and Antidiabetic Potential and Effect on Foodborne Bacterial Pathogens.

In the face of evolving healthcare challenges, the utilization of silver nanoparticles (AgNPs) has emerged as a compelling solution due to their unique properties and versatile applications. The aim of this study was the synthesis and characterization of novel AgNPs (SB-AgNPs and SG-AgNPs, respectively) using Salvia blepharophylla and Salvia greggii leaf extracts and the evaluation of their antimicrobial, antioxidant, and antidiabetic activities. Several analytical instrumental techniques were utilized for the characterization of SB-AgNPs and SG-AgNPs, including UV-visible (UV-Vis) spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transmission infrared (FT-IR) spectroscopy, energy-dispersive X-ray analysis (EDX), and X-ray diffraction (XRD). FTIR analysis identified various functional groups in the leaf extracts and nanoparticles, suggesting the involvement of phytochemicals as reducing and stabilizing agents. High-resolution TEM images displayed predominantly spherical nanoparticles with average sizes of 52.4 nm for SB-AgNPs and 62.5 nm for SG-AgNPs. Both SB-AgNPs and SG-AgNPs demonstrated remarkable antimicrobial activity against Gram-positive bacteria Staphylococcus aureus and Listeria monocytogenes and Gram-negative bacteria Salmonella typhimurium and Escherichia coli. SB-AgNPs and SG-AgNPs also exhibited 90.2 ± 1.34% and 89.5 ± 1.5% DPPH scavenging and 86.5 ± 1.7% and 80.5 ± 1.2% α-amylase inhibition, respectively, at a concentration of 100 μg mL-1. Overall, AgNPs synthesized using S. blepharophylla and Salvia greggii leaf extracts may serve as potential candidates for antibacterial, antioxidant, and antidiabetic agents. Consequently, this study provides viable solutions to mitigate the current crisis of antibiotic resistance and to efficiently combat antimicrobial infections and Type 2 diabetes.

Antioxidant, antidiabetic effects and polyphenolic contents of propolis from Siirt, Turkey.

Propolis, a natural product collected by honeybees from various plant sources, has gained significant attention due to its diverse bioactive compounds and potential therapeutic properties. To further explore its contents and biological activities, this study aimed to analyze the phenolic compounds in Siirt propolis extracts obtained using different solvents, namely ethanol, water, and ethanol-water mixtures. The primary objective of this research was to investigate the phenolic profile, as well as the antidiabetic and antioxidant activities of the propolis extracts. Chemical profiling of extracts was performed using LC-MS/MS. The antioxidant potential of the propolis extracts was evaluated through free radical scavenging methods, including DPPH and ABTS assays. As a result of these analyses, propolis extracts showed moderate radical scavenging potential with 13.86%-35.72% for DPPH and 33.62%-62.50% for ABTS at a concentration of 30 μg mL-1, respectively. This radical scavenging potential of the extracts sheds light on its ability to combat oxidative stress, which is implicated in the development of diabetes, and its potential effects on cellular health. Additionally, the study assessed the antidiabetic properties of the propolis extracts by examining their inhibition effects on α-amylase and α-glycosidase enzymes. Extracts with high phenolic content showed a high inhibitory effect against α-glucosidase with an IC50 of 5.72 ± 0.83 μg mL-1. This research provided significant findings regarding the potential use of propolis in the treatment of diabetes and related metabolic disorders.

Antifungal potential and chemical composition of Tagetes lunulata Ort. essential oil for the control of Trichophyton rubrum Malmsten

The essential oils of aromatic and medicinal plants are an important resource used to control several health conditions; however, information about their composition and antimicrobial activity is scarce. This study used a gas chromatography-mass spectrometry (GC-MS) to analyze the composition of the essential oil (EO) of Tagetes lunulata Ort., a Mexican endemic plant, known as wild cempaxúchitl. The major components of the EO include: verbenone (47.17%), α-pinene (10.93%), 1,1,1-Trifluoro-2-hexanone (9.63%), β-caryophyllene (6.10%), germacrene-D (4.99%), L-verbenone (4.89%), and E-tagetone (4.44%). The disk agar diffusion method was used to evaluate the antimicrobial activity of T. lunulata against Trichophyton rubrum (athlete's foot). A significant antimicrobial activity was observed with a ≥60% EO concentration. The dilution method was used to determine the minimum inhibitory concentration (MIC): 200 μg ml-1. The T. lunulata EO recorded a strong antimicrobial activity against T. rubrum; therefore, it is a natural alternative for the control of natural antifungals.

Thespesia lampas mediated green synthesis of silver and gold nanoparticles for enhanced biological applications

The present study investigated the synthesis and biological applications of green, economical, and multifunctional silver and gold nanoparticles (TSAgNPs and TSAuNPs) using the ethnomedical important medicinal plant Thespesia lampas for biological activities. Relatively higher levels of antioxidant components were measured in T. lampas compared to the well-known Adhatoda vasica, and Diplocyclos palmatus suggested the potential of T. lampas for the study. Synthesized TSAgNPs and TSAuNPs were characterized through UV-Vis, XRD, SEM-EDS, HR-TEM, SAED, and FTIR techniques. SEM revealed that TSAgNPs and TSAuNPs were predominantly spherical in shape with 19 ± 7.3 and 43 ± 6.3 nm crystal sizes. The sizes of TSAgNPs and TSAuNPs were found to be12 ± 4.8 and 45 ± 2.9 nm, respectively, according to TEM measurements. The FTIR and phytochemical analyses revealed that the polyphenols and proteins present in T. lampas may act as bio-reducing and stabilizing agents for the synthesis. Synthesized NPs exhibited enhanced scavenging properties for ABTS and DPPH radicals. TSAgNPs and TSAuNPs were able to protect DNA nicking up to 13.48% and 15.38%, respectively, from oxidative stress. TSAgNPs possessed efficient antibacterial activities in a concentration-dependent manner against human pathogenic bacteria, such as E. coli, B. subtilis, P. vulgaris, and S. typhi. Furthermore, TSAgNPs and TSAuNPs showed significant cytotoxicity against FaDu HNSCC grown in 2D at 50 and 100 μg mL-1. Tumor inhibitory effects on FaDu-derived spheroid were significant for TSAgNPs > TSAuNPs at 100 μg mL-1 in 3D conditions. Dead cells were highest largely for TSAgNPs (76.65% ± 1.76%), while TSAuNPs were non-significant, and Saq was ineffectively compared with the control. However, the diameter of the spheroid drastically reduced for TSAgNPs (3.94 folds) followed by TSAuNPs (2.58 folds), Saq (1.94 folds), and cisplatin (1.83 folds) at 100 μg mL-1. The findings of the study suggested the bio-competence of TSAgNPs and TSAuNPs as multi-responsive agents for antioxidants, DNA protection, antibacterial, and anti-tumor activities to provide a better comprehension of the role of phytogenic nanoparticles in healthcare systems.

Inhibitory activity to Fusarium spp. and control potential for wheat Fusarium crown rot of a novel succinate dehydrogenase inhibitor cyclobutrifluram.

Wheat Fusarium crown rot (FCR) is a serious problem primarily caused by Fusarium pseudograminearum, a pathogenic agent known to produce mycotoxins, including deoxynivalenol (DON). Cyclobutrifluram, a novel succinate dehydrogenase inhibitor devised by Syngenta, has immense potential to control both nematodes and Fusarium diseases. However, its efficacy in combating Fusarium species, its ability to prevent and reverse the detrimental effects of FCR, and its impact on the production of DON by F. pseudograminearum are yet to be fully ascertained. Cyclobutrifluram exhibited substantial inhibitory activity against Fusarium species, with half-maximal effective concentration values ranging from 0.0021-0.0647 μg mL-1 . It demonstrated significant inhibitory activity toward three developmental stages of F. pseudograminearum, F. graminearum and F. asiaticum. Furthermore, cyclobutrifluram showed both protective and curative activities against FCR and was rapidly absorbed by roots and transported to wheat stems and leaves. Cyclobutrifluram could also decrease DON production by F. pseudograminearum. This investigation has revealed the potential of cyclobutrifluram as a formidable candidate fungicide, particularly in its ability to effectively combat FCR and other Fusarium-related ailments. This novel compound has exceptional pathogen-fighting capabilities, coupled with remarkable systemic translocation properties and a notable ability to reduce the production of DON. © 2023 Society of Chemical Industry.

Evaluation of SYP-34773's resistance risk and its impact on the activity of mitochondrial respiratory electron transport chain complex I in Phytophthora litchii.

SYP-34773 is a low-toxicity pyrimidine amine compound, which was synthesized by modifying the lead compound diflumetorim. Previous literature has shown that it can strongly inhibit the mycelial growth of several important plant pathogens, including Phytophthora litchii. However, the resistance risk of SYP-34773 has not been reported for P. litchii. The mean effective concentration (EC50 ) value of SYP-34773 against the mycelial growth of 111 P. litchii isolates was 0.108 ± 0.008 μg mL-1 , which can be used as the baseline sensitivity for SYP-34773 resistance detection in the future. Six mutants were obtained from two parental strain through fungicide induction, whose resistance factors fell between 194- and 687-fold, with stability. Results regarding mycelial growth, sporangial production, sporangial germination, zoospore release, cystspore germination, and pathogenicity showed that the mutants' compound fitness index values were significantly lower than those of their parental isolate. Furthermore, there was no cross-resistance between SYP-34773 and diflumetorim in P. litchii. Significant inhibition of the mitochondrial complex I enzyme activity in two wild-type P. litchii isolates, but not in mutants, was observed upon treatment with SYP-34773. The resistance risk of SYP-34773 in P. litchii is moderate, and resistance management strategies should be adopted in field use. SYP-34773 is a mitochondrial complex I inhibitor, and SYP-34773-resistant P. litchii isolates did not show cross-resistance against diflumetorim. © 2023 Society of Chemical Industry.

Design, synthesis and in vitro anti-proliferative evaluation of new pyridine-2,3-dihydrothiazole/thiazolidin-4-one hybrids as dual CDK2/GSK3β kinase inhibitors.

Herein, the molecular hybridization drug discovery approach was used in the design and synthesis of twelve novel pyridine-2,3-dihydrothiazole hybrids (2a,b-5a,b and 13a,b-14a,b) and fourteen pyridine-thiazolidin-4-one hybrids (6a,b-12a,b) as anti-proliferative analogues targeting CDK2 and GSK3β kinase inhibition. Almost all of the newly synthesized hybrids, including their precursors (1a,b), were evaluated for their anti-proliferative activity against three human cancer cell lines-MCF-7, HepG2 and HEp-2-as well as normal Vero cell lines. Both compounds 1a (pyridine-thiourea precursor) and 8a (pyridine-5-acetyl-thiazolidin-4-one hybrid) exhibited excellent anti-proliferative activity against HEp-2 (IC50 = 7.5 μg mL-1, 5.9 μg mL-1, respectively). Additionally, 13a (pyridine-5-(p-tolyldiazenyl-2,3-dihydrothiazole)) hybrid demonstrated excellent anti-proliferative activity against HepG2 (IC50 = 9.5 μg mL-1), with an acceptable safety profile against Vero (<45% inhibition at 100 μg mL-1) in the cases of 8a and 13a alone. The three promising anti-proliferative hybrids (1a, 8a, 13a) were selected for the assessment of their in vitro inhibitory kinase activity against CDK2/GSK3β using roscovitine (IC50 = 0.88 μg mL-1) and CHIR-99021 (IC50 = 0.07 μg mL-1) as references, respectively. Compound 13a was the most potent dual CDK2/GSK3β inhibitor (IC50 = 0.396 μg mL-1, 0.118 μg mL-1, respectively) followed by 8a (IC50 = 0.675 μg mL-1, 0.134 μg mL-1, respectively), and the weakest was 1a. To elucidate the mechanism of the most potent anti-proliferative 13a hybrid, further cell cycle analysis was performed revealing that it caused G1 cell cycle arrest and induced apoptosis. Moreover, it resulted in an increase in Bax and caspase-3 with a decrease in Bcl-2 levels in HepG2 cells compared with untreated cells. Finally, in silico drug likeness/ADME prediction for the three potent compounds as well as a molecular docking simulation study were conducted in order to explore the binding affinity and interactions in the binding site of each enzyme, which inspired their usage as anti-proliferative leads for further modification.

Design, synthesis, and biological evaluation of pyrazole-ciprofloxacin hybrids as antibacterial and antibiofilm agents against Staphylococcus aureus.

In our continued efforts to tackle antibiotic resistance, a new series of pyrazole-ciprofloxacin hybrids were designed, synthesized, and evaluated for their antibacterial activity against Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Mycobacterium tuberculosis (Mtb). Most of the compounds exhibited good to excellent activities against S. aureus, and six compounds (7a, 7b, 7d, 7g, 7k, and 7p) exhibited higher or comparable activity (MIC = 0.125-0.5 μg mL-1) to ciprofloxacin (0.125 μg mL-1). Further, these selected compounds were non-toxic (CC50 ≥ 1000 μg mL-1) when evaluated for cell viability test against the Hep-G2 cell line. Three compounds (7a, 7d, and 7g) demonstrated excellent activity against ciprofloxacin-resistant S. aureus with MIC values ranging from 0.125-0.5 μg mL-1 and good antibiofilm activity. Among them, 7g displayed remarkable antibiofilm activity with an MBIC50 value of 0.02 μg mL-1, which is 50 times lower than ciprofloxacin (MBIC50 = 1.06 μg mL-1). A time-kill kinetics study indicated that 7g showed both concentration and time-dependent bactericidal properties. In addition, 7g effectively inhibited DNA-gyrase supercoiling activity at 1 μg mL-1 (8× MIC). Two compounds 7b and 7d exhibited the highest activity against Mtb with a MIC of 0.5 μg mL-1, while 7c showed the highest activity against P. aeruginosa with a MIC value of 2 μg mL-1. Molecular docking studies revealed that 7g formed stable interactions at the DNA active site.

Exploring beetroot (Beta vulgaris L.) for diabetes mellitus and Alzheimer's disease dual therapy: in vitro and computational studies.

This study explored the flavonoid-rich extract of beetroot (Beta vulgaris L.) for type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) dual therapy by using in vitro and molecular simulation studies. Flavonoid-rich extracts of B. vulgaris fruit were evaluated for their antidiabetic and anti-alzheimic activities. Molecular docking and dynamic simulation were performed to identify potential bioactive flavonoids with dual therapeutic effects on T2D and AD. Flavonoid-rich extracts of B. vulgaris fruit (IC50 = 73.062 ± 0.480 μg mL-1) had moderate activity against α-amylase compared to the standard acarbose (IC50 = 27.104 ± 0.270 μg mL-1). Compared with acarbose, flavonoid-rich extracts of B. vulgaris fruit had appreciable activity against α-glucosidase (IC50 = 17.389 ± 0.436 μg mL-1) (IC50 = 37.564 ± 0.620 μg mL-1). For AChE inhibition, flavonoid-rich extracts of B. vulgaris fruit exhibited (p < 0.0001) inhibitory activity (IC50 = 723.260 ± 5.466 μg mL-1), albeit weaker than that of the standard control, galantamine (IC50 = 27.950 ± 0.122 μg mL-1). Similarly, flavonoid-rich extracts of B. vulgaris fruit showed considerable (p < 0.0001) inhibitory effects on BChE (IC50 = 649.112 ± 0.683 μg mL-1). In contrast, galantamine (IC50 = 23.126 ± 0.683 μg mL-1) is more potent than the extracts of B. vulgaris fruit. Monoamine oxidase (MAO) activity increased in FeSO4-induced brain damage. In contrast, flavonoid-rich extracts of B. vulgaris fruit protected against Fe2+-mediated brain damage by suppressing MAO activity in a concentration-dependent manner. HPLC-DAD profiling of the extracts identified quercetrin, apigenin, rutin, myricetin, iso-quercetrin, p-coumaric acid, ferulic acid, caffeic acid, and gallic acid. Molecular docking studies revealed quercetrin, apigenin, rutin, iso-queretrin, and myricetin were the top docked bioactive flavonoids against the five top target proteins (α-amylase, α-glucosidase AchE, BchE, and MAO). Molecular dynamic simulations revealed that the complexes formed remained stable over the course of the simulation. Collectively, the findings support the prospect of flavonoid-rich extracts of B. vulgaris root functioning as a dual therapy for T2D and AD.

Design and synthesis of novel multi-target tetrabromophthalimides as CBS and Topo-II inhibitors and DNA intercalators.

Microtubules are highly dynamic structures and constitute a crucial component of the cellular cytoskeleton. Besides, topoisomerases (Topo) play a fundamental role in maintaining the appropriate structure and organization of DNA. On the other hand, dual mechanism drug candidates for cancer treatment primarily aim to enhance the efficacy of cancer treatment and potentially overcome drug resistance. Hence, this work was tailored to design and synthesize new multi-target tetrabromophthalimide derivatives (2a-2k) that are capable of inhibiting the colchicine binding site (CBS) and topoisomerase II (Topo-II). The conducted in vitro studies showed that compound 2f showed the lowest IC50 value (6.7 μg mL-1) against the MDA-MB-468 cancer cell line. Additionally, compound 2f prompted upregulation of pro-apoptotic markers (caspases 3, 7, 8, and 9, Bax and p53). Moreover, some anti-apoptotic proteins (MMP2, MMP9, and BCL-2) were downregulated by compound 2f treatment. Besides, the colchicine binding assay showed that compounds 2f and 2k displayed promising inhibitory potential with IC50 values of 1.92 and 4.84 μg mL-1, respectively, in comparison with colchicine (1.55 μg mL-1). Furthermore, the Topo-II inhibition assay displayed the prominent inhibitory potential of compound 2f with an IC50 value of 15.75 μg mL-1, surpassing the IC50 of etoposide (20.82 μg mL-1). Cell cycle analysis revealed that compound 2f induced cell cycle arrest at both the G0-G1 and G2-M phases. The new candidates were docked against both the CBS (PDB ID: 5XIW) and Topo-II (PDB ID: 5CDP) targets to investigate their binding interactions and affinities as well. Accordingly, the synthesized compounds could serve as promising multi-target anticancer candidates with eligible apoptotic activity.

Design, synthesis and potent anti-pancreatic cancer activity of new pyrazole derivatives bearing chalcone, thiazole and thiadiazole moieties: gene expression, DNA fragmentation, cell cycle arrest and SAR.

Less than 5% of pancreatic cancer patients survive for more than five years after diagnosis. Therefore, there is an urgent need for novel therapeutic drugs to treat pancreatic cancer. Herein, we report the synthesis and full characterization of fifteen novel pyrazole derivatives bearing chalcone (4-10), thiazole (16-19) and thiadiazole (23-26) moieties. All the newly synthesized pyrazole derivatives were tested in vitro as anti-cancer agents against pancreatic cancer (PaCa-2), breast cancer (MCF-7), prostate cancer (PC3), and normal cell lines (BJ1). Three pyrazolyl-chalcone derivatives (4, 5, and 7) and a pyrazolyl-thiadiazole derivative (25) showed potent anti-cancer activity against the PaCa-2 cell line with IC50 values of 13.0, 31.5, 24.9, and 5.5 μg mL-1, respectively, compared with doxorubicin (IC50 = 28.3 μg mL-1). Compound 25 showed potent anti-cancer activity against the PC3 cell line with an IC50 value of 11.8 μg mL-1. In contrast, compounds 4, 5 and 7 are safer against the normal human-cell line (BJ1) with IC50 values of 74.2, 76.6 and 81.1 μg mL-1, respectively, compared with compound 25, which has an IC50 value of 23.7 μg mL-1. The mechanism of action of compounds 4, 5 and 7 against pancreatic cancer cells was studied by investigating gene expression, DNA fragmentation, comet assay and flow cytometry experiments using doxorubicin as a reference drug. Moreover, the structure-activity relationship between the structures of these compounds and their biological properties was discussed.

Synthesis, antimicrobial activity and application of polymers of praseodymium complexes based on pyridine nitrogen oxide.

The traditional pyridine nitrogen oxide-based antimicrobial agents are often associated with health risks due to heavy metal enrichment. To mitigate this concern, we synthesized two novel complexes, Pr2(mpo)6(H2O)2 and Pr(hpo)(mpo)2(H2O)2, and integrated rare-earth salts, Hhpo (2-hydroxypyridine-N-oxide) and Nampo (2-mercapto-pyridine-N-oxide sodium salt). These complexes were characterized through infrared analysis, elemental analysis, thermogravimetric analysis, and X-ray crystallographic analysis. Our comparative analyses demonstrate that the synthesized rare-earth complexes exhibit stronger antimicrobial activity against Staphylococcus aureus (S. aureus ATCC6538) and Escherichia coli (E. coli ATCC25922) compared to the ligands and rare-earth salts alone. Quantitative results revealed the lowest inhibitory concentrations of the two complexes against S. aureus ATCC6538 and E. coli ATCC25922 at 3.125 μg mL-1, 6.25 μg mL-1, 3.125 μg mL-1 and 6.25 μg mL-1, respectively. Preliminary investigations indicated that the antibacterial mechanism of these complexes involved promoting intracellular substance exudation to achieve antibacterial effects. Incorporation of these complexes into polymeric antimicrobial films resulted in a potent antimicrobial effect, achieving a 100% inhibition rate against S. aureus ATCC6538 and E. coli ATCC25922 at a low addition level of 0.6 wt%. Our results suggest that nitrogen oxide-based praseodymium complexes have potential for various antimicrobial applications.

Novel phenylthiazoles with a tert-butyl moiety: promising antimicrobial activity against multidrug-resistant pathogens with enhanced ADME properties.

The structure-activity relationship of a new tert-butylphenylthiazole series, with a pyrimidine linker, was investigated. We wished to expand knowledge of this novel class of antibiotics by generating 21 new derivatives bearing ≥2 heteroatoms in their side chains. Their activity was examined against isolates of methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. Two compounds with 1,2-diaminocyclohexane as a nitrogenous side chain showed promising activity against the highly infectious MRSA USA300 strain, with a minimum inhibitory concentration (MIC) of 4 μg mL-1. One of these two compounds demonstrated potent activity against C. difficile, with a MIC of 4 μg mL-1. Moderate activities against a C. difficile strain with a MIC of 8 μg mL-1 were noted. Some new compounds possessed antifungal activity against a wild fluconazole-resistant C. albicans strain, with MIC values of 4-16 μg mL-1. ADME and metabolism-simulation studies were performed for the most promising compound and compared with lead compounds. Our results revealed that one compound possessed greater penetration of bacterial membranes and metabolic resistance, which aided a longer duration of action against MRSA.

Innovation of 6-sulfonamide-2H-chromene derivatives as antidiabetic agents targeting α-amylase, α-glycosidase, and PPAR-γ inhibitors with in silico molecular docking simulation.

A new series of 2-imino or 2-oxo-2H-chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 μg mL-1. Additionally, the IC50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC50 values of 1.76 ± 0.01 and 1.08 ± 0.02 μM, respectively, compared to Acarbose (IC50 = 0.43 ± 0.01 μM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC50 values of 0.548 ± 0.02 and 2.44 ± 0.09 μg mL-1, compared to Acarbose (0.604 ± 0.02 μg mL-1). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC50 values of 3.152 ± 0.03 and 3.706 ± 0.32 μg mL-1, respectively, compared to Pioglitazone (4.884 ± 0.29 μg mL-1). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket.

Activity of fungicide cyclobutrifluram against Fusarium fujikuroi and mechanism of the pathogen resistance associated with point mutations in FfSdhB, FfSdhC2 and FfSdhD

Rice bakanae disease (RBD) is a devastating plant disease caused by Fusarium fujikuroi. This study aimed to evaluate the potential of cyclobutrifluram, a novel succinate dehydrogenase inhibitor (SDHI), to control RBD, and determine the risk and mechanism of resistance to cyclobutrifluram in F. fujikuroi. In vitro experiments showed that cyclobutrifluram significantly inhibited mycelial growth and spore germination, and altered the morphology of mycelia and conidia. Treatment with cyclobutrifluram significantly decreased mycotoxin production and increased cell membrane permeability in F. fujikuroi. The baseline sensitivity of 72 F. fujikuroi isolates to cyclobutrifluram was determined using mycelial growth and spore germination inhibition assays, which revealed EC50 values of 0.0114 – 0.1304 μg mL-1 and 0.0012 – 0.016 μg mL-1, with mean EC50 values of 0.0410 ± 0.0470 μg mL-1 and 0.0038 ± 0.0015 μg mL-1, respectively. Pot experiments demonstrated that the protective effect of cyclobutrifluram against F. fujikuroi was more significant than that of phenamacril and azoxystrobin, indicating that cyclobutrifluram is a promising antifungal agent for the control of RBD. Six cyclobutrifluram-resistant mutants of F. fujikuroi were obtained via fungicide adaptation. Moreover, these mutants exhibited weaker fitness than their parental isolate and positive cross-resistance with other SDHI fungicides, including pydiflumetofen and penflufen; however, no cross-resistance was detected with other classes of fungicides, including phenamacril, fludioxonil, prochloraz, or azoxystrobin. These results indicated that the resistance risk of F. fujikuroi to cyclobutrifluram might be moderate. Sequencing analysis revealed that mutations, including H248D in FfSdhB, A83V in FfSdhC2, and S106F and E166K in FfSdhD, contributed to resistance, which was confirmed by molecular docking and homologous replacement experiments. The results suggest a high potential for cyclobutrifluram to control RBD and a moderate resistance risk of F. fujikuroi to cyclobutrifluram, which are meaningful findings for the scientific application of cyclobutrifluram.

Cinnamon extracts, trans-cinnamaldehyde and trans-cinnamic acid inhibit HDAC 1 activity.

Histone deacetylase (HDAC) enzymes play a key role in cell function and are implicated in several diseases such as inflammation, cancer, and neurodegeneration. Studies on natural products have revealed their potential and have led to increased research on natural HDAC inhibitors. Since the progression of these diseases is a prolonged process, dietary supplements and nutraceuticals consisting of plant extracts may be beneficial against HDAC related diseases. Beyond nutritional purposes, cinnamon (Cinnamomum cassia (L.) J. Presl), as a regularly consumed dietary additive due to its rich flavor, may present co-benefits during lifelong use. In this study, cinnamon extracts of differing polarities, trans-cinnamaldehyde and trans-cinnamic acid were evaluated for HDAC 1 inhibitory activity. The total phenol and flavonoid contents were quantified by spectrophotometry, while cinnamaldehyde and cinnamic acid analyses were performed using UPLC-DAD, ESI-MS/MS. Ethanol and dichloromethane extracts yielded the highest cinnamaldehyde and cinnamic acid contents of 389.17 mg per g extract and 11.85 mg per g extract, respectively. The essential oil (IC50: 51.11 μg ml-1) and 70% ethanol extract (IC50: 107.90 μg ml-1) showed the most potent HDAC 1 inhibitory activity. Individually, cinnamaldehyde and cinnamic acid were determined to have IC50 values of 7.58 μg ml-1 and 9.15 μg ml-1, respectively. As the 70% ethanol extract was able to yield remarkably lower cinnamaldehyde and cinnamic acid amounts, the potential of other moderately polar phenolic compounds for HDAC 1 inhibitory activity was revealed. The essential oil and 70% ethanol extracts of Cinnamomum cassia bark can be further evaluated in future studies for use in products against HDAC 1 related diseases.

Highly selective solid-liquid extraction of microplastic mixtures as a pre-preparation tool for quantitative nuclear magnetic resonance spectroscopy studies.

Despite various developments in the application of quantitative nuclear magnetic resonance (qNMR) spectroscopy toward microplastics in recent years, this method still lacks suitable sample preparation and fractionation procedures. As this poses a crucial obstacle for its utilisation on environmental samples, which contain various mixtures of polymers along with other matrix substances, this research aims to address this missing link by presenting an easy-to-apply procedure based on common laboratory equipment. The process selectively separates microplastics from inorganic constituents while performing the necessary fractionation of different types of microplastics prior to qNMR analysis. It allows subsequent quantification of polystyrene (PS), polybutadiene rubber (BR), polymethylmethacrylate (PMMA), polyvinylchloride (PVC), polyethylene terephthalate (PET) and polyamide (PA) from a single sample, establishing recovery rates greater than 88% for all tested polymer types. Additionally, we extended our previous qNMR protocol to include two common polymer types: polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN), achieving limits of detection down to 1.76 μg ml-1 and 12.53 μg ml-1 as well as limits of quantification down to 5.88 μg ml-1 and 41.78 μg ml-1, respectively. Thus, the qNMR method presented herein is now applicable to eight abundant polymer types, allowing the quantification of up to three different types simultaneously.

Unveiling the multifaceted antiproliferative efficacy of Cichorium endivia root extract by dual modulation of apoptotic and inflammatory genes, inducing cell cycle arrest, and targeting COX-2.

Chicory (Cichorium endivia L. divaricatum) is a renowned medicinal plant traditionally used for various ailments, yet the pharmacological potential of its roots, particularly in terms of antitumor activity, remains elusive. In the present study, we explore, for the first time, the metabolomic profile of ethanolic extract from Cichorium endivia roots (CIR) and further unveil its antiproliferative potential. The untargeted phytochemical analysis UPLC/T-TOF-MS/MS identified 131 metabolites in the CIR extract, covering acids, amino acids, flavonoids, alkaloids, nucleotides, and carbohydrates. The antiproliferative activity of the CIR extract was tested in 14 cancer cell lines, revealing significant cytotoxicity (IC50: 2.85-29.15 μg mL-1) and a high selectivity index. Among the cells examined, the CIR extract recorded the most potent antiproliferative activity and selectivity toward HepG2 and Panc-1 cells, with an IC50 of 2.85 μg mL-1 and 3.86 μg mL-1, respectively, and SI > 10. Insights into the mode of action of the antiproliferative activity revealed that CIR extract induces cell arrest in the S phase while diminishing cell distribution in the G0/G1 and G2/M phases in HepG-2 and Panc-1 cells. Flow cytometric and RT-PCR analysis revealed that the CIR extract significantly triggers apoptosis and modulates the expression of pro-apoptotic and anti-apoptotic genes. Furthermore, the CIR extract exhibited a pronounced anti-inflammatory activity, as evidenced by down-regulating key cytokines in LPS-induced RAW 264.7 cells and selectively inhibiting the COX-2 enzyme. Finally, the CIR extract showed a robust total antioxidant capacity, together with potent free radicals and metal scavenging properties, highlighting its role in alleviating oxidative stress. Taken together, this study highlights the multifaceted therapeutic potential of CIR extract as a natural-based antitumor supplement.

Detection of toxic cypermethrin pesticides in drinking water by simple graphitic electrode modified with Kraft lignin@Ni@g-C3N4 nano-composite.

The detrimental effects of widespread pesticide application on the health of living organisms highlight the urgent need for technological advancements in monitoring pesticide residues at trace levels. This study involves the synthesis of a distinctive sensing material, KL@Ni@g-C3N4, which comprises nanocomposites of graphitic carbon nitride with Kraft lignin and nickel. The prepared samples were characterized using FT-IR, PXRD, TEM, SEM, and EDX techniques. The KL@Ni@g-C3N4 nanocomposite was drop-cast on a graphite electrode. Subsequently, this fabricated electrode was used to detect cypermethrin (CYP) residues in drinking water. The redox properties of the fabricated sensors were evaluated using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The limit of detection (LOD) of the fabricated sensor was determined to be 0.026 μg mL-1, which is below the maximum residual limits of CYP in the environment (0.5 μg mL-1) and within the acceptable range for food products (∼0.05 to 0.2 μg mL-1). Therefore, this study proposes a promising alternative to conventional methods for detecting pesticides in drinking water.