EC50 Values Research Articles

Computational Modeling Oriented Substructure Splicing Application in the Identification of Thiazolidine Derivatives as Potential Low Honeybee Toxic Neonicotinoids.

With the aim of identifying novel neonicotinoid insecticides with low bee toxicity, a series of compounds bearing thiazolidine moiety, which has been shown to be low bee toxic, were rationally designed through substructure splicing strategy and evaluated insecticidal activities. The optimal compounds A24 and A29 exhibited LC50 values of 30.01 and 17.08 mg/L against Aphis craccivora, respectively. Electrophysiological studies performed on Xenopus oocytes indicated that compound A29 acted on insect nAChR, with EC50 value of 50.11 μM. Docking binding mode analysis demonstrated that A29 bound to Lymnaea stagnalis acetylcholine binding protein through H-bonds with the residues of D_Arg55, D_Leu102, and D_Val114. Quantum mechanics calculation showed that A29 had a higher highest occupied molecular orbit (HOMO) energy and lower vertical ionization potential (IP) value compared to the high bee toxic imidacloprid, showing potentially low bee toxicity. Bee toxicity predictive model also indicated that A29 was nontoxic to honeybees. Our present work identified an innovative insecticidal scaffold and might facilitate the further exploration of low bee toxic neonicotinoid insecticides.

Macrocyclic Azapeptide Nitriles: Structure-Based Discovery of Potent SARS-CoV-2 Main Protease Inhibitors as Antiviral Drugs.

Given the crucial role of the main protease (Mpro) in the replication cycle of SARS-CoV-2, this viral cysteine protease constitutes a high-profile drug target. We investigated peptidomimetic azapeptide nitriles as auspicious, irreversibly acting inhibitors of Mpro. Our systematic approach combined an Mpro active-site scanning by combinatorially assembled azanitriles with structure-based design. Encouraged by the bioactive conformation of open-chain inhibitors, we conceptualized the novel chemotype of macrocyclic azanitriles whose binding mode was elucidated by cocrystallization. This strategy provided a favorable entropic contribution to target binding and resulted in the development of the extraordinarily potent Mpro inhibitor 84 with an IC50 value of 3.23 nM and a second-order rate constant of inactivation, kinac/Ki, of 448,000 M-1s-1. The open-chain Mpro inhibitor 58, along with the macrocyclic compounds 83 and 84, a broad-spectrum anticoronaviral agent, demonstrated the highest antiviral activity with EC50 values in the single-digit micromolar range. Our findings are expected to promote the future development of peptidomimetic Mpro inhibitors as anti-SARS-CoV-2 agents.

Toxoplasma replication is inhibited by MMV676477 without development of resistance.

Protozoan parasites cause life-threatening infections in both humans and animals, including agriculturally significant livestock. Available treatments are typically narrow spectrum and are complicated by drug toxicity and the development of resistant parasites. Protozoan tubulin is an attractive target for the development of broad-spectrum antimitotic agents. The Medicines for Malaria Pathogen Box compound MMV676477 was previously shown to inhibit replication of kinetoplastid parasites, such as Leishmania amazonensis and Trypanosoma brucei, and the apicomplexan parasite Plasmodium falciparum by selectively stabilizing protozoan microtubules. In this report, we show that MMV676477 inhibits intracellular growth of the human apicomplexan pathogen Toxoplasma gondii with an EC50 value of ~50 nM. MMV676477 does not stabilize vertebrate microtubules or cause other toxic effects in human fibroblasts. The availability of tools for genetic studies makes Toxoplasma a useful model for studies of the cytoskeleton. We conducted a forward genetics screen for MMV676477 resistance, anticipating that missense mutations would delineate the binding site on protozoan tubulin. Unfortunately, we were unable to use genetics to dissect target interactions because no resistant parasites emerged. This outcome suggests that future drugs based on the MMV676477 scaffold would be less likely to be undermined by the emergence of drug resistance.

Hydrogeochemical and GIS Analysis of Groundwater Quality for Drinking and Irrigation Purposes in Kuzhithuraiyar Sub-Basin, Kanniyakumari District, Tamil Nadu, India

A hydrogeochemical analysis was conducted to find the suitability of the groundwater for drinking and irrigation purposes in the Kuzhithuraiyar sub-basin, Kanniyakumari district, Tamil Nadu, India. 48 groundwater samples were collected from the different locations of the study area during both the pre- and postmonsoon periods. This study assesses the groundwater quality for drinking and irrigation purposes based on the analytical results, water quality index, Wilcox plot, and irrigation parameters such as electrical conductance, Kelly’s ratio, sodium absorption ratio values, magnesium hazards, bicarbonate, and the residual sodium carbonate index. The pH values ranged from 8.5 to 6.5, suggesting generally acceptable conditions. TDS concentrations range from 24 to 1277 mg/L, whereas EC values range from 37.50 to 1996 μS/cm. It is observed from the collected samples that the pre-monsoon water samples TDS’ values were exceeded the recommended TDS limits than postmonsoon samples. Water quality indices indicate that 50% of premonsoon samples and 48% of postmonsoon samples are suitable for drinking. In total, 10% of samples are admissible to a doubtful category before and after the monsoon, 6% are good to permissible during the monsoon, and 84% are good to permissible. Kelly’s ratio shows that 56% and 48% of samples collected during the post- and premonsoon are suitable for irrigation, respectively, whereas the remaining samples are not. Due to magnesium hazards, 40% and 44% of pre- and postmonsoon samples are not suitable for irrigation. Overall, the postmonsoon samples exceeded the permissible TDS limit (1000 mg/L) by 10% and the premonsoon samples by 6. 13% of samples obtained after the monsoon and 19% collected before the monsoon have a potential salinity greater than three, indicating that these samples are unacceptable. The sustaining water quality and mitigating possible hazards in the Kuzhithuraiyar sub-basin require continuous monitoring and focused measures.

The effect of leachates on the physical and engineering properties of subsoil varies across different rock types and depth layers

Waste disposal on land is a major environmental issue that affects groundwater through soil. The aim of this study is to evaluate and compare the physical and engineering properties of subsoil at varying depths from different dumpsites and to determine the effects of leachates and parent rock types on these soil properties. Thirty-six subsoil samples were obtained from twelve trial pit profiles at depths of 0.5 m, 1.0 m and 1.5 m respectively. These soil samples were subjected to both geotechnical index and strength tests. Grain size analysis, linear shrinkage, CBR and compaction tests revealed that many of the soil samples from dumpsites and their environs met the criteria of a good landfill material. All the soil samples have low permeability that ranges from 2.07 × 10–6 to 1.49 × 10–4. Liquid limit, plasticity index and MDD values were higher in the control samples while the dumpsite soils became more permeable. The results of grain size analysis, linear shrinkage and CBR revealed that there was no significant difference in the properties of dumpsite and control soils. All the soil samples have TDS and EC values below 1000 ppm and 1000 µS/cm, except for trial pit 1, suggesting that the soil has a low risk of leaching contaminants into groundwater. For analysis of variance and Pearson’s correlation coefficient, the P values of some parameters such as pH, EC, TDS, CBR, OMC, MDD, SG, LS, PI and LL were significant at a 0.05 level of significance. The following pairwise parameters: pH-MDD, TDS-CBR, EC-CBR, OMC-MDD and TDS-EC recorded strong positive correlation values for the three dumpsites. The statistical analyses reveal that the soil's properties were only slightly influenced by parent rock types and can be used to limit contaminant flow into the groundwater in the short term.

Synthesis of Planar Chiral Compounds Containing α-Amino Phosphonates for Antiplant Virus Applications against Potato Virus Y.

An unprecedented study of the application of planar chiral compounds in antiviral pesticide development is reported. A class of multifunctional planar chiral ferrocene derivatives bearing α-amino phosphonate moieties was synthesized. These compounds, exhibiting superior optical purities, were subsequently subjected to antiviral evaluations against the notable plant pathogen potato virus Y (PVY). The influence of the absolute configurations of the planar chiral compounds on their antiviral bioactivities was significant. A number of these enantiomerically enriched planar chiral molecules demonstrated superior anti-PVY activities. Specifically, compound (Sp, R)-9n displayed extraordinary curative activities against PVY, with a 50% maximal effective concentration (EC50) of 216.11 μg/mL, surpassing the efficacy of ningnanmycin (NNM, 272.74 μg/mL). The protective activities of compound (Sp, R)-9n had an EC50 value of 152.78 μg/mL, which was better than that of NNM (413.22 μg/mL). The molecular docking and defense enzyme activity tests were carried out using the planar chiral molecules bearing different absolute configurations to investigate the mechanism of their antiviral activities against PVY. (Sp, R)-9n, (Sp, R)-9o, and NMM all showed stronger affinities to the PVY-CP than the (Rp, S)-9n. Investigations into the mechanisms revealed that the planar chiral configurations of the compounds played pivotal roles in the interactions between the PVY-CP molecules and could augment the activities of the defense enzymes. This study contributes substantial insights into the role of planar chirality in defending plants against viral infections.

Structure-Activity Relationships toward the Identification of a High-Potency Selective Human Toll-like Receptor-7 Agonist.

Toll-like receptor (TLR)-7 agonists are immunostimulatory vaccine adjuvants. A systematic structure-activity relationship (SAR) study of TLR7-active 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine led to the identification of a potent hTLR7-specific p-hydroxymethyl IMDQ 23 with an EC50 value of 0.22 μM. The SAR investigation also resulted in the identification of TLR7 selective carboxamide 12 with EC50 values of 0.32 μM for hTLR7 and 18.25 μM for hTLR8. In the vaccination study, TLR7-specific compound 23 alone or combined with alum (aluminum hydroxide wet gel) showed adjuvant activity for a spike protein immunogen in mice, with enhanced anti-spike antibody production. Interestingly, the adjuvant system comprising carboxamide 12 and alum showed prominent adjuvant activity with high levels of IgG1, IgG2b, and IgG2c in immunized mice, confirming a balanced Th1/Th2 response. In the absence of any apparent toxicity, the TLR7 selective agonists in combination with alum may make a suitable vaccine adjuvant.

New Carbothioamide and Carboxamide Derivatives of 3-Phenoxybenzoic Acid as Potent VEGFR-2 Inhibitors: Synthesis, Molecular Docking, and Cytotoxicity Assessment.

Because of the well-established link between angiogenesis and tumor development, the use of antiangiogenic therapeutics, such as those targeting VEGFR-2, presents a promising approach to cancer treatment. In the current study, a set of five hydrazine-1-- carbothioamide (compounds 3a-e) and three hydrazine-1-carboxamide derivatives (compounds 4a-c) were successfully synthesized from 3-phenoxybenzoic acid. These compounds were specially created as antiproliferative agents with the goal of targeting cancer cells by inhibiting VEGFR-2 tyrosine kinase. The new derivatives were synthesized by conventional organic methods, and their structure was versified by IR, 1HNMR, 13CNMR, and mass spectroscopy. In silico investigation was carried out to identify the compounds' target, molecular similarity, ADMET, and toxicity profile. The cytotoxic activity of the prepared compounds was evaluated in vitro against three human cancer cell lines (DLD1 colorectal adenocarcinoma, HeLa cervical cancer, and HepG2 hepatocellular carcinoma). The effects of the leading compound on cell cycle progression and apoptosis induction were investigated by flow cytometry, and the specific apoptotic pathway triggered by the treatment was evaluated by RT-PCR and immunoblotting. Finally, the inhibitory activities of the new compounds against VEGFR-2 was measured. The designed derivatives exhibited comparable binding positions and interactions to the VEGFR-2 binding site to that of sorafenib (a standard VEGFR-2 tyrosine kinase inhibitor), as determined by molecular docking analysis. Compound 4b was the most cytotoxic compound, achieving the lowest IC50 against HeLa cells. Compound 4b, a strong representative of the synthesized series, induced cell cycle arrest at the G2/M phase, increased the proportion of necrotic and apoptotic HeLa cells, and activated caspase 3. The EC50 value of compound 4b against VEGFR-2 kinase activity was comparable to sorafenib's. Overall, the findings suggest that compound 4b has a promising future as a starting point for the development of new anticancer drugs.

Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors.

Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.

From Epimedium to Neuroprotection: Exploring the Potential of Wushanicaritin

Epimedium has been used for functional foods with many beneficial functions to human health. Wushanicaritin is one of the most important chemicals int Epimedium. This study investigated the neuroprotective effects of wushanicaritin and potential underlying mechanisms. The results demonstrated that wushanicaritin possessed superior intercellular antioxidant activity compared to icaritin. Wushanicaritin, with an EC50 value of 3.87 μM, showed better neuroprotective effect than quercetin, a promising neuroprotection agent. Wushanicaritin significantly reversed lactate dehydrogenase release, reactive oxygen species generation, cell apoptosis, and mRNA expression related to cell apoptosis and oxidative defense, in glutamate-induced PC-12 cells. Wushanicaritin could also maintain the enzymatic antioxidant defense system and mitochondrial function. The suppression of caspase-3 activation and amelioration of mitochondrial membrane potential loss and nucleus morphology changes were involved in the antiapoptotic effect of wushanicaritin. These findings suggested that wushanicaritin possesses excellent intercellular antioxidant and neuroprotective activities, showing potential promise in functional foods.

Development of a label‐free, impedance‐based biosensor to identify harmful effects of pesticides on insect cells

AbstractInsects are a major part of the planet's ecosystem and their vital role as pollinators for agriculture is undisputed. Alongside factors as climate change or loss of habitats, rising use of pesticides emerges as a key threat to insect populations. For fighting this man‐made problem, development of an easy, fast, sensitive, and non‐invasive biosensor for determining pesticide toxicity may help to ban harmful substances and formulations. Here, a biosensor based on Sf21 (Spodoptera frugiperda) insect cells as sensors and electric cell‐substrate impedance sensing (ECIS) as physical transducer is described. Sf21 cell suspensions and well‐defined pesticide solutions were mixed immediately before seeding on planar gold‐film electrodes. The capacitance at 20 kHz was recorded as a function of time as a measurand for cell adhesion providing dose–response profiles of pesticide impact. For future in‐field applications, decoupling of the cell culture routines from the actual cytotoxicity assay is mandatory. Thus, suspensions of Sf21 cells were cryopreserved at –80°C in the wells of multielectrode arrays and thawed anytime for conducting the assays. Five pesticides were tested for their concentration‐dependent cytotoxicity expressed as EC50 values by ECIS and validated using the well‐established WST‐1 cell viability assay. Results were found to be in good agreement. Our studies revealed cytotoxic effects of some pesticides sold for home usage far below the recommended concentration and were found to be more toxic than formulations sold for agricultural industry only.

Novel Sulfoximine Derivatives Containing Cyanoguanidine and Nitroguanidine Moieties: Design, Synthesis, and Bioactivities.

A total of 32 novel sulfoximines bearing cyanoguanidine and nitroguanidine moieties were designed and synthesized by a rational molecule design strategy. The bioactivities of the title compounds were evaluated and the results revealed that some of the target compounds possessed excellent antifungal activities against six agricultural fungi, including Sclerotinia sclerotiorum, Fusarium graminearum, Phytophthora capsici, Botrytis cinerea, Rhizoctonia solani, and Pyricularia grisea. Among them, compounds 8e1 and 8e4 exhibited significant efficacy against P. grisea with EC50 values of 2.72 and 2.98 μg/mL, respectively, which were much higher than that of commercial fungicides boscalid (47.95 μg/mL). Interestingly, in vivo assays determined compound 8e1 possessed outstanding activity against S. sclerotiorum with protective and curative effectiveness of 98 and 95.6% at 50 μg/mL, which were comparable to those of boscalid (93.2, 91.9%). The further preliminary mechanism investigation disclosed that compound 8e1 could damage the structure of the cell membrane of S. sclerotiorum, increase its permeability, and suppress its growth. Overall, the findings enhanced that these novel sulfoximine derivatives could be potential lead compounds for the development of new fungicides.

Ru(II) Oligothienyl Complexes with Fluorinated Ligands: Photophysical, Electrochemical, and Photobiological Properties.

A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-f][1,10]phenanthroline (IP-nT) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb)2(IP-nT)]2+ scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy)3]2+. Ru-1T-Ru-4T have additional oxidations due to the nT group and additional reductions due to the 4,4'-btfmb ligands. Ru-2T-Ru-4T also exhibit nT-based reductions. Ru-4T exhibits two oxidations and eight reductions within the potential window of -3 to +1.5 V. The lowest-lying triplets (T1) for Ru-0T-2T are metal-to-ligand charge-transfer (3MLCT) excited states with lifetimes around 1 μs, whereas T1 for Ru-3T-4T is longer-lived (∼20-24 μs) and of significant intraligand charge-transfer (3ILCT) character. Phototoxicity toward melanoma cells (SK-MEL-28) increases with n, with Ru-4T having a visible EC50 value as low as 9 nM and PI as large as 12,000. Ru-3T and Ru-4T retain some of this activity in hypoxia, where Ru-4T has a visible EC50 as low as 35 nM and PI as high as 2900. Activity over six biological replicates is consistent and within an order of magnitude. These results demonstrate the importance of lowest-lying 3ILCT states for phototoxicity and maintaining activity in hypoxia.

NT-proBNP for Predicting All-Cause Death and Heart Transplant in Children and Adults with Heart Failure.

Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) concentration is a heart failure (HF) biomarker in adults and children. Its prognostic value for HF-related events has been established only in adults. Therefore, weaimed to test the hypothesis that plasma NT-proBNP concentrations predicted the risk of heart transplantation or death in children with HF. We studied the medical records of 109 children with HF enrolled in the IBM Watson Explorys database and from 150 children enrolled in the Pediatric Cardiomyopathy Registry (PCMR). Nonlinear regression was used to assess the relationship between plasma NT-proBNP concentrations and the risk of events in the two cohorts. All children in the PCMR cohort had dilated cardiomyopathy. The Explorys cohort also included children with congenital cardiovascular malformations. Median plasma NT-proBNP concentrations were 1250pg/mL and 184pg/mL in the Explorys and PCMR cohorts, respectively. The percentage of deaths/heart transplantations was 7%/22%, over 2years in the Explorys cohort and 3%/16% over 5years in the PCMR cohort. Mean estimates of plasma NT-proBNP concentration indicative of half-maximum relative risk for events (EC50 values) at 2 and 5years were 3730pg/mL and 4199pg/mL, respectively, values both close to the mean of 3880pg/mL established for adults with HF. The plasma NT-proBNP concentration is suitable for estimating relative risk of mortality and heart transplantation in children with HF, independent of etiology and shows similar relations to clinical outcomes as in adults, indicating its likely value as a surrogate marker both for adult and pediatric HF.ClinicalTrials.gov Identifiers: NCT00005391 (May 26, 2000), NCT01873976 (June 10, 2013).

Synthesis, antifungal activity and action mechanism of novel citral amide derivatives against Rhizoctonia solani.

Rice sheath blight caused by Rhizoctonia solani is a severe threat to the yield and quality of rice. Due to the unscientific abuse of common fungicides causing resistance and environmental issues, the development of new fungicides is necessary. In this study, we used citral as the lead compound, designed and synthesized a series of novel citral amide derivatives, and evaluated their antifungal activity and mode of action against R. solani. Bioassay results indicated that the antifungal activities of most citral amide derivatives against R. solani were significantly improved compared to citral, with EC50 values ranging from 9.50-27.12 mg L-1. Among them, compound d21 containing the N-(pyridin-4-yl)carboxamide group exhibited in vitro and in vivo fungicidal activities, with curative effects at 500 mg L-1 as effectively as the commercial fungicide validamycin·bacillus. Furthermore, d21 prolonged the lag phase of the growth curve of R. solani, reduced the amount of growth, and inhibited sclerotium germination and formation. Mechanistically, d21 deformed the mycelia, increased cell membrane permeability, and inhibited the activities of antioxidant and tricarboxylic acid cycle (TCA)-related enzymes. Metabolome analysis showed the abundance of some energy-related metabolites within R. solani increased, and simultaneously the antifungal substances secreted by itself reduced. Transcriptome analysis showed that most genes encoding ATP-binding cassette (ABC) transporters and peroxisomes upregulated after the treatment of d21 and cell membrane destruction. This study indicates that novel citral amide derivatives possess antifungal activity against R. solani and are expected to develop an alternative option for chemical control of rice sheath blight. © 2024 Society of Chemical Industry.

Identification and Characterization of Colletotrichum truncatum and C. destructivum Causing Stem Rot of White Clover in China.

White clover (Trifolium repens L.) is an excellent quality forage legume species with superior planting efficiency, which reduces the cost of artificial weeding and nitrogen fertilizer inputs, and has feeding and economic value. However, from June to September 2022, severe stem rot affected the yield and quality of white clover crops in Harbin, Heilongjiang Province, China. The aim of this study was to identify the causative agents of the disease. Overall, Colletotrichum truncatum (6 isolates) and C. destructivum (10 isolates) were obtained from rotten white clover stems and identified based on morpho-molecular characteristics and phylogenetic analyses. Pathogenicity tests of the isolates revealed that C. destructivum had a higher pathogenicity to white clover than C. truncatum. In addition, all isolates were highly pathogenic to broad bean, fodder soybean, soybean, pak choi, and chickpea, were pathogenic to mint, and did not infect corn, wheat, or cilantro. C. destructivum and C. truncatum isolates were very sensitive to tebuconazole and pyraclostrobin, with EC50 values of 0.54 to 0.70 μg/ml and 0.42 to 0.62 μg/ml, respectively, efficacies ranging between 93.2 to 94.9% and 90.2 to 95.2% at 600 μg/ml and 450 μg/ml, respectively, and EC90 values of 1.88 to 13.36 μg/ml and 1.32 to 23.39 μg/ml, respectively. Therefore, intercropping of host and nonhost plants and chemicals can be considered to control stem rot in white clover. These results provide a basis for controlling C. destructivum and C. truncatum in white clover in China.

Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024

Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (−)-nigrosporine C (−)-3, together with eight known compounds (4–11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1–3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher’s method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 μmol/L and without cytotoxicity in a concentration of 100.0 μmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 μmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 μmol/L.

Drymariamides A-J, Antiadipogenic Cyclopeptides Incorporating Noncanonical Amino Acids from Drymaria cordata.

Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A-J (1-10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey's method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1-10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 μM.

Plant-assisted green preparation of silver nanoparticles using leaf extract of Dalbergia sissoo and their antioxidant, antibacterial and catalytic applications.

Plant-mediated preparation of silver nanoparticles (AgNPs) is thought to be a more economical and environmentally benign process in comparison to physical and chemical synthesis methods. In the present study, the aqueous leaf extract of Dalbergia sissoo was prepared and utilized to reduce silver ion (Ag+) during the green synthesis of silver nanoparticles (DL-AgNPs). The formation of DL-AgNPs was verified using UV-Vis spectra, exhibiting the surface plasmon resonance (SPR) band at around 450nm. FT-IR analysis revealed the kinds of phytochemicals that serve as reducing and capping agents while DL-AgNPs are being synthesized. Analysis of scanning electron microscope (SEM) and high-resolution transmission electron microscopy (HR-TEM) images verified the development of spherical and oval-shaped DL-AgNPs, with sizes ranging from 10 to 25nm. The stability and particle size distribution of synthesized DL-AgNPs were ensured by zeta potential and DLS (dynamic light scattering) investigations. Additionally, X-ray diffraction (XRD) analysis confirmed the crystalline nature of DL-AgNPs. In antioxidant experiments, DL-AgNPs demonstrated significant scavenging capacities of DPPH and ABTS radicals with EC50 values of 51.32 and 33.32μg/mL, respectively. The antibacterial activity of DL-AgNPs was shown to be significant against harmful bacteria, with a maximum zone of inhibition (21.5 ± 0.86mm) against Staphylococcus aureus. Furthermore, DL-AgNPs exhibited effective catalytic activity to degrade environment-polluting dyes (methylene blue, methyl orange, and Congo red) and toxic chemicals (p-nitrophenol). The results of all these studies suggested that DL-AgNPs made from the leaf extract of Dalbergia sissoo have merit for application in the environmental and biomedical fields.

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors.

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 μg/mL that was superior to that of the agricultural fungicide boscalid (2.2 μg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 μM that was superior to that of boscalid (7.9 μM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.