Foliar Application of Rhizobium leguminosarum bv. viciae Strain 33504-Borg201 Promotes Faba Bean Growth and Enhances Systemic Resistance Against Bean Yellow Mosaic Virus Infection.

The bean yellow mosaic virus (BYMV) is one of the most serious economic diseases affecting faba bean crop production. Rhizobium spp., well known for its high nitrogen fixation capacity in legumes, has received little study as a possible biocontrol agent and antiviral. Under greenhouse conditions, foliar application of molecularly characterized Rhizobium leguminosarum bv. viciae strain 33504-Borg201 to the faba bean leaves 24 h before they were infected with BYMV made them much more resistant to the disease while also lowering its severity and accumulation. Furthermore, the treatment promoted plant growth and health, as evidenced by the increased total chlorophyll (32.75 mg/g f.wt.) and protein content (14.39 mg/g f.wt.), as well as the improved fresh and dry weights of the plants. The protective effects of 33504-Borg201 greatly lowered the levels of hydrogen peroxide (H2O2) (4.92 µmol/g f.wt.) and malondialdehyde (MDA) (173.72 µmol/g f.wt.). The antioxidant enzymes peroxidase (1.58 µM/g f.wt.) and polyphenol oxidase (0.57 µM/g f.wt.) inhibited the development of BYMV in plants treated with 33504-Borg201. Gene expression analysis showed that faba bean plants treated with 33504-Borg201 had higher amounts of pathogenesis-related protein-1 (PR-1) (3.28-fold) and hydroxycinnamoyl-CoA quinate hydroxycinnamoyltransferase (4.13-fold) than control plants. These findings demonstrate the potential of 33,504-Borg201 as a cost-effective and eco-friendly method to protect faba bean plants against BYMV. Implementing this approach could help develop a simple and sustainable strategy for protecting faba bean crops from the devastating effects of BYMV.

Pathological characterization and management of Lasiodiplodia theobromae, a hemi-biotroph with an interkingdom host range.

Heart rot disease, caused by Lasiodiplodia theobromae, is destructive for date palms and other woody plants. The disease was reported in several oasis in Egypt, and the pathogen was found in association with infected trees suffering die-back and rachis blight. Seven phylogenetically distinct fungal isolates were selected, and their pathogenicity was confirmed on date palms. The isolates exhibited variable degrees of virulence on inoculated leaves, which confirms the variation. We examined the antifungal effect of microbial bioagents and plant extracts on heart rot disease. The isolates of Trichoderma spp. gave moderate reduction of the pathogen's linear growth (40-60%), while their exudates were ultimately ineffective. Bacillus spp. isolates, except for B. megaterium, were more effective against spore germination as they gave 80-90% reduction on average. Among the examined plant extracts garlic sap gave 98.67% reduction of linear growth followed by artemisia (15.5%) and camphor (24.8%). The extraction methods greatly influenced the antifungal efficiency of each extract as exposure to organic solvents significantly decreased the efficiency of all extracts, while hot water extraction negatively affected garlic sap only. Successful bioagents and plant extracts were further assayed for the suppression of heart rot disease on date palms. Both T. album and T. harzianum gave comparable degrees of suppression as by commercial fungicides. In addition, treatment before or during pathogen inoculation was the most effective as it significantly enhanced the expression of defense-related enzymes. Our findings suggest bio-pesticides possessing a dual role in disease suppression and defense boosters for date palms suffering heart rot disease.

Green chemometric-assisted UV-spectrophotometric methods for the determination of favipiravir, cefixime and moxifloxacin hydrochloride as an effective therapeutic combination for COVID-19; application in pharmaceutical form and spiked human plasma.

As pharmaceutical analysis progresses towards environmental sustainability, there is a growing need to enhance the safety and health conditions for analysts. Consequently, the incorporation of chemometrics into environmentally friendly analytical methods represents a promising approach. Favipiravir, cefixime, and moxifloxacin hydrochloride have been currently used in COVID-19 treatment. In this study, we develop spectrophotometric methods depending on chemometric based models to measure the levels of favipiravir, cefixime, and moxifloxacin hydrochloride in pharmaceutical preparations and spiked human plasma. It is challenging to determine favipiravir, cefixime, and moxifloxacin simultaneously because of overlap in their UV absorption spectra. Two advanced chemometric models, partial least square (PLS) and genetic algorithm (GA), have been developed to provide better predictive abilities in spectrophotometric determination of the drugs under study. The described models were created using a five-level, three-factor experimental design. The outcomes of the models have been thoroughly assessed and interpreted, and a statistical comparison with recognized values has been taken into consideration. The analytical eco-scale and the green analytical procedure index (GAPI) evaluation methods were also utilized to determine how environmentally friendly the mentioned models were. The outcomes demonstrated how well the models described complied with the environmental requirements.

Novel 2-[thio]acetamide linked quinazoline/1,2,4-triazole/chalcone hybrids: Design, synthesis, and anticancer activity as EGFR inhibitors and apoptotic inducers.

Novel triazoloquinazolines carrying the 2-[thio]acetamide entity (4 and 5a-d) and triazoloquinazoline/chalcone hybrids incorporating the 2-[thio]acetamide linker (8a-b and 9a-f) were developed as anticancer candidates. NCI screening of the synthesized compounds at 10 µM concentration displayed growth inhibition not only up to 99.74% as observed for 9a but also a lethal effect could be achieved as stated for compounds 9c (RPMI-8226 and HCT-116) and 8b, 9a, and 9e on the HCT-116 cell line. The antiproliferative activity was determined for the chalcone series on three cell lines: RPMI-8226, HCT-116, and MCF-7. Compounds 8b, 9a, 9b, and 9f were the most active ones. To understand the mechanistic study, the inhibitory effect on the epidermal growth factor receptor (EGFR) kinase was evaluated. The results stated that the activity of compound 8b (IC50 = 0.07 µM) was near that of the reference drug erlotinib (IC50 = 0.052 µM) whereas compound 9b (IC50 = 0.045 µM) was found to be more potent than erlotinib. Both compounds 8b and 9b were selected for cell cycle analysis and apoptotic assays. Moreover, molecular docking results of the selected chalcone hybrids showed high binding scores and good binding affinities especially for 8b and 9b, which were consistent with the biological activity (EGFR).

Dual COX-2 and 15-LOX inhibition study of novel 4-arylidine-2-mercapto-1-phenyl-1H-imidazolidin-5(4H)-ones: Design, synthesis, docking, and anti-inflammatory activity.

Novel arylidene-5(4H)-imidazolone derivatives 4a-r were designed and evaluated as multidrug-directed ligands, that is, inflammatory, proinflammatory mediators, and reactive oxygen species (ROS) inhibitors. All of the tested compounds showed cyclooxygenase (COX)-1 inhibitory effect more than celecoxib and less than indomethacin and also demonstrated an improved inhibitory activity against 15-lipoxygenase (15-LOX). Compounds 4f, 4l, and 4p exhibited COX-2 selectivity comparable to that of celecoxib, while 4k was the most selective COX-2 inhibitor. Interestingly, the screened results showed that compound 4k exhibited a superior inhibition effect against 15-LOX and was found to be the most selective COX-2 inhibitor over celecoxib, whereas compound 4f showed promising COX-2 and 15-LOX inhibitory activities besides its inhibitory effect against ROS production and its lowering effect of both tumor necrosis factor-α and interleukin-6 levels by ∼80%. Moreover, compound 4f attenuated the lipopolysaccharide-mediated increase in NF-κB activation in RAW 264.7 macrophages. The preferred binding affinity of these molecules was confirmed by docking studies. We conclude that arylidene-5(4H)-imidazolone scaffolds provide promising hits for developing new synthons with anti-inflammatory and antioxidant activities.

Trichoderma afroharzianum TRI07 metabolites inhibit Alternaria alternata growth and induce tomato defense-related enzymes.

Identifying a viable substitute for the limited array of current antifungal agents stands as a crucial objective in modern agriculture. Consequently, extensive worldwide research has been undertaken to unveil eco-friendly and effective agents capable of controlling pathogens resistant to the presently employed fungicides. This study explores the efficacy of Trichoderma isolates in combating tomato leaf spot disease, primarily caused by Alternaria alternata. The identified pathogen, A. alternata Alt3, was isolated and confirmed through the ITS region (OQ888806). Six Trichoderma isolates were assessed for their ability to inhibit Alt3 hyphal growth using dual culture, ethyl acetate extract, and volatile organic compounds (VOCs) techniques. The most promising biocontrol isolate was identified as T. afroharzianum isolate TRI07 based on three markers: ITS region (OQ820171), translation elongation factor alpha 1 gene (OR125580), and RNA polymerase II subunit gene (OR125581). The ethyl acetate extract of TRI07 isolate was subjected to GC-MS analysis, revealing spathulenol, triacetin, and aspartame as the main compounds, with percentages of 28.90, 14.03, and 12.97%, respectively. Analysis of TRI07-VOCs by solid-phase microextraction technique indicated that the most abundant compounds included ethanol, hydroperoxide, 1-methylhexyl, and 1-octen-3-one. When TRI07 interacted with Alt3, 34 compounds were identified, with major components including 1-octen-3-one, ethanol, and hexanedioic acid, bis(2-ethylhexyl) ester. In greenhouse experiment, the treatment of TRI07 48 h before inoculation with A. alternata (A3 treatment) resulted in a reduction in disease severity (16.66%) and incidence (44.44%). Furthermore, A3 treatment led to improved tomato growth performance parameters and increased chlorophyll content. After 21 days post-inoculation, A3 treatment was associated with increased production of antioxidant enzymes (CAT, POD, SOD, and PPO), while infected tomato plants exhibited elevated levels of oxidative stress markers MDA and H2O2. HPLC analysis of tomato leaf extracts from A3 treatment revealed higher levels of phenolic acids such as gallic, chlorogenic, caffeic, syringic, and coumaric acids, as well as flavonoid compounds including catechin, rutin, and vanillin. The novelty lies in bridging the gap between strain-specific attributes and practical application, enhancing the understanding of TRI07's potential for integrated pest management. This study concludes that TRI07 isolate presents potential natural compounds with biological activity, effectively controlling tomato leaf spot disease and promoting tomato plant growth. The findings have practical implications for agriculture, suggesting a sustainable biocontrol strategy that can enhance crop resilience and contribute to integrated pest management practices.

Eco-friendly novel deconvoluted synchronous spectrofluorimetric approach for the determination of favipiravir, levodropropizine and moxifloxacin hydrochloride as an effective therapeutic combination for COVID-19; application in laboratory prepared mixtures and spiked human plasma.

In this work, a green, fast, and simple synchronous spectrofluorimetric approach has been developed to simultaneously determine favipiravir, levodropropizine, and moxifloxacin hydrochloride as co-administered medications for COVID-19 treatment in pure form and spiked human plasma. The synchronous fluorescence spectroscopy technique to analyze the studied drugs at Δλ = 110 nm enabled the determination of levodropropizine at 360 nm. Then, applying Fourier Self-Deconvolution to each spectra to measure favipiravir and moxifloxacin hydrochloride at peak amplitudes of 431 nm and 479 nm, respectively, without any interference. Favipiravir, levodropropizine, and moxifloxacin hydrochloride could be sensitively determined using the described approach over concentration ranges of 20-300 ng/mL, 10-600 ng/mL, and 50-500 ng/mL, respectively. The method's validation was carried out effectively in accordance with guidelines recommended by the ICH. Finally, the Eco-scale and Green Analytical Procedure Index (GAPI) techniques have been used to evaluate the greenness of the proposed method.

GC-MS profiling and evaluation of acute oral toxicity, anti-tumour, antimicrobial and antioxidant activities of Croton socotranus Balf.f. aerial parts: in-vitro, in-vivo and in-silico studies.

Croton socotranus Balf.f. shrub is widely used traditionally in Asia as an anti-infective. The study was conducted for metabolite profiling, oral acute toxicity and antioxidant studies, antimicrobial activity and anticancer effect against human hepatoma (HepG2), breast cancer (MCF-7) and rhabdomyosarcoma (RD) cells. Gas chromatography-mass spectrometry analysis revealed the presence of 39 compounds, predominantly comprising fatty acids (57.76%), sesquiterpenes (24.56%) and triterpenes (9.54%). The n-hexane fraction exhibited promising antimicrobial activity and displayed a potent anti-tumour effect against HepG2, MCF-7 and RD cells with IC50 values of 3.4, 6.5 and 7.1 µg/mL, respectively. Histological examination revealed significant morphological changes consistent with the changes observed in the apoptotic mechanism of action. The molecular docking study provided insights into the rational binding modes of the identified compounds with phosphoinositide 3-kinase and poly(ADP-ribose)polymerase-1 enzymes. Our findings suggest the potential of C. socotranus as a valuable source of antimicrobial and anticancer agents.

Identification, Sequencing, and Molecular Analysis of RNA2 of Artichoke Italian Latent Virus Isolates from Known Hosts and a New Host Plant Species.

Despite its first description in 1977 and numerous reports of its presence in various plant species in many countries, the molecular information available in GenBank for artichoke Italian latent virus (AILV) is still limited to a single complete genome sequence (RNA1 and 2) of a grapevine isolate (AILV-V) and a partial portion of the RNA2 sequence from an isolate of unknown origin and host. Here, we report the results of molecular analyses conducted on the RNA2 of some AILV isolates, sequenced for the first time in this study, together with the first-time identification of AILV in a new host plant species, namely chard (Beta vulgaris subsp. vulgaris), associated with vein clearing and mottling symptoms on leaves. The different AILV isolates sequenced were from artichoke (AILV-C), gladiolus (AILV-G), Sonchus (AILV-S), and chard (AILV-B). At the molecular level, the sequencing results of the RNA2 segments showed that AILV-C, AILV-G, AILV-S, and AILV-B had a length of 4629 nt (excluding the 3' terminal polyA tail), which is one nt shorter than that of the AILV-V reported in GenBank. A comparison of the RNA2 coding region sequences of all the isolates showed that AILV-V was the most divergent isolate, with the lowest sequence identities of 83.2% at the nucleotide level and 84.7% at the amino acid level. Putative intra-species sequence recombination sites were predicted among the AILV isolates, mainly involving the genomes of AILV-V, AILV-C, and AILV-B. This study adds insights into the variability of AILV and the occurrence of recombination that may condition plant infection.

Phytochemical analysis and insight into insecticidal and antifungal activities of Indian hawthorn leaf extract.

Fungicides or insecticides are popular means of controlling a variety of pathogens and insect pests; however, they can cause harmful effects on both human health and the environment. Different researchers have suggested using plant extracts, which have shown promise in managing fungi and insects. The purpose of this investigation was to explore the antifungal activities of an acetone extract made from the leaves of Indian Hawthorn (HAL) against phytopathogens that are known to harm maize crops, Fusarium verticillioides (OQ820154) and Rhizoctonia solani (OQ820155), and to evaluate the insecticidal property against Aphis gossypii Glover aphid. The HAL extract demonstrated significant antifungal activity against the two fungal pathogens tested, especially at the high dose of 2000 µg/mL. Laboratory tests on the LC20 of HAL extract (61.08 mg/L) versus buprofezin 25% WP (0.0051 mg/L) were achieved on A. gossypii Glover. HAL extract diminished the nymph's production over 72 h and their total reproductive rate. This extract was like buprofezin 25% WP in decreasing the daily reproductive rate, reproductive period, and mean survival percentage. Nevertheless, the newly-born nymphs of treated females with HAL extract attained the highest reduction in survival percentage at 46.00%. Equalized prolongations on the longevity of nymphs to 9.33, 8.33, and 7 days and the total life cycle to 15.00, 14.00, and 12.67 days were realized by HAL extract, buprofezin 25% WP, and the control, respectively. The olfactory choice test on the aphids showed the minimum attraction rate to HAL extract. The HPLC of HAL extract comprised an abundance of phenolic compounds (ferulic acid, gallic acid, 4-hydroxybenzoic acid, salicylic acid, ellagic acid, and pyrogallol), and the concentrations of these compounds vary widely, with salicylic acid being the most concentrated at 25.14 mg/mL. Among the flavonoids, epicatechin has the highest concentration at 11.69 mg/mL. The HAL extract GC-MS consists of various organic compounds, including sesquiterpenes, cyclopropenes, fatty acids, steroids, alcohols, ketones, esters, bufadienolides, opioids, and other organic compounds. The most abundant compounds in the sample are n-hexadecanoic acid (12.17%), followed by 5α, 7αH, 10α-eudesm-11-en-1α-ol (9.43%), and cis-13-octadecenoic acid (5.87%). Based on the findings, it can be inferred that the HAL extract may be a viable option for plants to combat both fungal and insect infestations. This presents an encouraging prospect for utilizing a natural and sustainable approach toward long-term pest management in plants.

Exploring the antibacterial potential of plant extracts and essential oils against Bacillus thermophilus in beet sugar for enhanced sucrose retention: a comparative assessment and implications.

Sugar beet is one of the greatest sources for producing sugar worldwide. However, a group of bacteria grows on beets during the storage process, leading to a reduction in sucrose yield. Our study focused on identifying common bacterial species that grow on beets during manufacturing and contribute to sucrose loss. The ultimate goal was to find a potential antibacterial agent from various plant extracts and oils to inhibit the growth of these harmful bacteria and reduce sucrose losses. The screening of bacterial species that grow on beet revealed that a large group of mesophilic bacteria, such as Bacillus subtilis, Leuconostoc mesenteroides, Pseudomonas fluorescens, Escherichia coli, Acinetobacter baumannii, Staphylococcus xylosus, Enterobacter amnigenus, and Aeromonas species, in addition to a dominant thermophilic species called Bacillus thermophilus, were found to be present during the manufacturing of beets. The application of 20 plant extracts and 13 different oils indicated that the extracts of Geranium gruinum, Datura stramonium, and Mentha spicata were the best antibacterials to reduce the growth of B. thermophilus with inhibition zones equal to 40, 39, and 35 mm, respectively. In contrast, the best active oils for inhibiting the growth of B. thermophilus were Mentha spicata and Ocimum bacilicum, with an inhibitory effect of 50 and 45 mm, respectively. RAPD-PCR with different primers indicated that treating sugar juice with the most effective oils against bacteria resulted in new recombinant microorganisms, confirming their roles as strong antibacterial products. The characterization of Mentha spicata and Ocimum bacilicum oils using GC/MS analysis identified cis-iso pulegone and hexadecanoic acid as the two main bioactive compounds with potential antibacterial activity. An analysis of five genes using DD-PCR that have been affected due to antibacterial activity from the highly effective oil from Mentha spicata concluded that all belonged to the family of protein defense. Our findings indicate that the application of these pure antibacterial plant extracts and oils would minimize the reduction of sucrose during sugar production.

Magic shotgun approach to anti-inflammatory pharmacotherapy: Synthesis of novel thienopyrimidine monomers/heterodimer as dual COX-2 and 15-LOX inhibitors endowed with potent antioxidant activity.

Emerging evidence points to the intertwining framework of inflammation and oxidative stress in various ailments. We speculate on the potential impact of the magic shotgun approach in these ailments as an attempt to mitigate the drawbacks of current NSAIDs. Hence, we rationally designed and synthesized new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine monomers/heterodimer as dual selective COX-2/15-LOX inhibitors with potent antioxidant activity. The synthesized compounds were challenged with diverse in vitro biological assays. Regarding the monomeric series, compound 5k exerted the highest COX-2 inhibitory activity (IC50 = 0.068 µM, SI = 160.441), while compound 5i showed the highest 15-LOX inhibitory activity (IC50 = 1.97 µM). Surpassing the most active monomeric members, the heterodimer 11 stemmed as the most potent and selective one in the whole study (COX-2 IC50 = 0.065 µM, SI = 173.846, 15-LOX IC50 = 1.86 µM). Heterodimer design was inspired by the cross-talk between the partner monomers of the COX-2 isoform. Moreover, some of our synthesized compounds could significantly reverse the LPS-enhanced production of ROS and proinflammatory cytokines (IL-6, TNF-α, and NO) in RAW 264.7 macrophages. Again, the heterodimer showed the strongest suppressor activity against ROS (IC50 = 18.79 µM) and IL-6 (IC50 = 4.15 µM) production outperforming the two references, celecoxib and diclofenac. Regarding NO suppressor activity, compound 5j (IC50 = 18.62 µM) surpassed the two references. Only compound 5a significantly suppressed TNF-α production (IC50 = 19.68 µM). Finally, molecular modeling simulated the possible binding scenarios of our synthesized thienopyrimidines within the active sites of COX-2 and 15-LOX. These findings suggest that those novel thienopyrimidines are promising leads showing pharmacodynamics synergy against the selected targets.

Zinc Oxide Nanoparticles Biosynthesized by Eriobotrya japonica Leaf Extract: Characterization, Insecticidal and Antibacterial Properties.

Zinc oxide nanoparticles (ZnO-NPs) have gained significant attention in nanotechnology due to their unique properties and potential applications in various fields, including insecticidal and antibacterial activities. The ZnO-NPs were biosynthesized by Eriobotrya japonica leaf extract and characterized by various techniques such as UV-visible (UV-vis) spectrophotometer, X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and zeta potential analysis. The results of SEM revealed that NPs were irregular and spherical-shaped, with a diameter between 5 and 27 nm. Meanwhile, DLS supported that the measured size distributions were 202.8 and 94.7 nm at 11.1° and 90.0°, respectively, which supported the polydisperse nature of NPs, and the corresponding zeta potential was -20.4 mV. The insecticidal activity of the produced ZnO-NPs was determined against the adult stage of coleopteran pests, Sitophilus oryzae (Linnaeus) (Curculionidae) and Tribolium castaneum (Herbst) (Tenebrionidae). The LC50 values of ZnO-NPs against adults of S. oryzae and T. castaneum at 24 h of exposure were 7125.35 and 5642.65 µg/mL, respectively, whereas the LC90 values were 121,824.56 and 66,825.76 µg/mL, respectively. Moreover, the biosynthesized nanoparticles exhibited antibacterial activity against three potato bacterial pathogens, and the size of the inhibition zone was concentration-dependent. The data showed that the inhibition zone size increased with an increase in the concentration of nanoparticles for all bacterial isolates tested. The highest inhibition zone was observed for Ralstonia solanacearum at a concentration of 5 µg/mL, followed by Pectobacterium atrosepticum and P. carotovorum. Eventually, ZnO-NPs could be successfully used as an influential agent in pest management programs against stored-product pests and potato bacterial diseases.

Protective Activity of Rhizobium leguminosarum bv. viciae Strain 33504-Mat209 against Alfalfa Mosaic Virus Infection in Faba Bean Plants.

The application of Rhizobium spp., nitrogen-fixing plant growth-promoting rhizobacteria, as biocontrol agents to enhance systemic disease resistance against plant viral infections is a promising approach towards achieving sustainable and eco-friendly agriculture. However, their potential as antivirals and biocontrol agents is less studied. Herein, the capability of Rhizobium leguminosarum bv. viciae strain 33504-Mat209 was evaluated to promote plant growth and enhance faba bean systemic resistance against alfalfa mosaic virus (AMV) infection. Under greenhouse conditions, the soil inoculation with 3504-Mat209 resulted in notable improvements in growth and an increase in chlorophyll content. This led to a marked decrease in the disease incidence, severity, and viral accumulation level by 48, 74, and 87%, respectively. The protective effect of 33504-Mat209 was linked to significant decreases in non-enzymatic oxidative stress indicators, specifically H2O2 and MDA. Additionally, there were significant increases in the activity of reactive oxygen species scavenging enzymes, such as peroxidase (POX) and polyphenol oxidase (PPO), compared to the virus treatment. The elevated transcript levels of polyphenolic pathway genes (C4H, HCT, C3H, and CHS) and pathogenesis-related protein-1 were also observed. Out of 18 detected compounds, HPLC analysis revealed that 33504-Mat209-treated plants increased the accumulation of several compounds, such as gallic acid, chlorogenic acid, catechin, pyrocatechol, daidzein, quercetin, and cinnamic acid. Therefore, the ability of 33504-Mat209 to promote plant growth and induce systemic resistance against AMV infection has implications for utilizing 33504-Mat209 as a fertilizer and biocontrol agent. This could potentially introduce a new strategy for safeguarding crops, promoting sustainability, and ensuring environmental safety in the agricultural sector. As far as we know, this is the first study of biological control of AMV mediated by Rhizobium spp. in faba bean plants.

Productivity and Phytochemicals of Asclepias curassavica in Response to Compost and Silver Nanoparticles Application: HPLC Analysis and Antibacterial Activity of Extracts.

The application of compost and metallic nanoparticles has a significant impact on the productivity and chemical composition of horticulture plants. In two subsequent growing seasons, 2020 and 2021, the productivity of Asclepias curassavica L. plants treated with various concentrations of silver nanoparticles (AgNPs) and compost was assessed. In the pot experiments, the soil was amended with 25% or 50% compost, and the plants were sprayed with 10, 20, and 30 mg/L of AgNPs. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), and dynamic light scattering (DLS) were used to characterize AgNPs. The TEM measurements of AgNPs showed that the particles had spherical forms and ranged in size from roughly 5 to 16 nm. Leaf methanol extracts (LMEs) were prepared from the treated plants and assayed against the growth of two soft rot bacteria, Dickeya solani and Pectobacterium atrosepticum. The maximum plant height, diameter, number of branches/plant, total fresh weight (g), total dry weight (g), and leaf area (cm2) was recorded when levels of 25% compost + AgNPs 20 mg/L, 25% compost, or 50% + AgNPs 20 mg/L, 25% compost + AgNPs 30 mg/L or 50% compost + AgNPs 20 mg/L, 50% compost + AgNPs 20 mg/L, 50% compost + AgNPs 30 or 20 mg/L, and 25% compost + AgNPs 30 mg/L, respectively, were applied. The plants treated with 25% or 50% compost + 30 mg/L AgNPs showed a high chlorophyll content, while the plants treated with 50% compost + AgNPs 30 mg/L or 20 mg/L showed the highest extract percentages. The highest inhibition zones (IZs), 2.43 and 2.2 cm, against the growth of D. solani were observed in the LMEs (4000 mg/L) extracted from the plants treated with compost (v/v) + AgNPs (mg/L) at the levels of 50% + 30 and 25% + 30, respectively. The highest IZs, 2.76 and 2.73 cm, against the growth of P. atrosepticum were observed in the LMEs (4000 mg/L) extracted from the plants treated at the levels of 50% + 30 and 25% + 30, respectively. Several phenolic compounds such as syringic acid, p-coumaric acid, chlorogenic acid, cinnamic acid, ellagic acid, caffeic acid, benzoic acid, gallic acid, ferulic acid, salicylic acid, pyrogallol, and catechol, as well as flavonoid compounds such as 7-hydroxyflavone, naringin, rutin, apigenin, quercetin, kaempferol, luteolin, hesperidin, catechin, and chrysoeriol, were identified in the LMEs as analyzed by HPLC with different concentrations according to the treatment of compost + AgNPs used for the plants. In conclusion, the specific criteria that were utilized to measure the growth of A. curassavica revealed the novelty of compost and AgNPs combination treatments, particularly at a concentration of 50% compost + AgNPs 30 mg/L or 20 mg/L, which is better for the growth and phytochemical production of A. curassavica in the field.

Antiviral Activity of Biosynthesized Silver Nanoparticles from Pomegranate (Punica granatum L.) Peel Extract against Tobacco Mosaic Virus.

Tobacco mosaic virus (TMV) is a major pathogen affecting tomato plants worldwide. The efficacy of silver nanoparticles (Ag-NPs) mediated by Punica granatum biowaste peel extract in mitigating the negative impact of TMV infection on tomato growth and oxidative stress was investigated through scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-Visible (UV-Vis) spectrophotometer, X-ray Diffraction (XRD), dynamic light scattering (DLS), zeta potential, energy-dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectra (FTIR). Results of SEM analysis of green Ag-NPs revealed the presence of condensed spherical or round NPs with diameters ranging between 61 and 97 nm. TEM confirmed the SEM results and showed round-shaped Ag-NPs with an average size of 33.37 ± 12.7 nm. The elemental analysis (EDX) of prepared Ag-NPs revealed the presence of elemental Ag as a major peak (64.43%) at 3-3.5 KeV. The FTIR revealed several functional groups on the prepared Ag-NPs, for which three treatment strategies for Ag-NP applications were evaluated in the greenhouse study and compared to inoculated TMV and control plants: pre-infection treatment (TB), post-infection treatment (TA), and dual treatment (TD). The results showed that the TD strategy is the most effective in improving tomato growth and reducing viral replication, whereas all Ag-NP treatments (TB, TA, and TD) were found to significantly increase expression of the pathogenesis-related (PR) genes PR-1 and PR-2, as well as polyphenolic compounds, HQT, and C4H genes compared to control plants. In contrast, the flavonoid content of tomato plants was not affected by the viral infection, while the phenolic content was significantly reduced in the TMV group. Furthermore, TMV infection led to a significant increase in oxidative stress markers MDA and H2O2, as well as a reduction in the enzymatic activity of the antioxidants PPO, SOD, and POX. Our results clearly showed that the application of Ag-NPs on TMV-infected plants reduces virus accumulation, delays viral replication in all treatments, and greatly enhances the expression of the CHS gene involved in flavonoid biosynthesis. Overall, these findings suggest that treatment with Ag-NPs may be an effective strategy to mitigate the negative impact of TMV infection on tomato plants.

Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines.

A new series of thieno[2,3-d]pyrimidine derivatives 4, 5, 6a-o, and 11 was designed and synthesized starting from cyclohexanone under Gewald condition with the aim to develop multitarget-directed ligands (MTDLs) having anti-inflammatory properties against both 15-LOX and COX-2 enzymes. Moreover, the potential of the compounds against the proinflammatory mediators NO, ROS, TNF-α, and IL-6 were tested in LPS-activated RAW 264.7 macrophages. Compound 6o showed the greatest 15-LOX inhibitory effect (IC50 = 1.17 µM) which was superior to that of the reference nordihydroguaiaretic acid (NDGA, IC50 = 1.28 µM); meanwhile, compounds 6h, 6g, 11, and 4 exhibited potent activities (IC50 = 1.29-1.77 µM). The ester 4 (SI = 137.37) and the phenyl-substituted acetohydrazide 11 (SI = 132.26) showed the highest COX-2 selectivity, which was about 28 times more selective than the reference drug diclofenac (SI = 4.73), however, it was lower than that of celecoxib (SI = 219.25). Interestingly, compound 6o, which showed the highest 15-LOX inhibitory activity and 5 times higher COX-2 selectivity than diclofenac, showed a greater poteny in reducing NO (IC50 = 7.77 µM) than both celecoxib (IC50 = 22.89 µM) and diclofenac (IC50 = 25.34), but comparable activity in inhibiting TNF-α (IC50 = 11.27) to diclofenac (IC50 = 10.45 µM). Similarly, compounds 11 and 6h were more potent in reducing TNF-α and IL6 levels than diclofenac, meanwhile, compound 4 reduced ROS, NO, IL6, and TNF-α levels with comparable potency to the reference drugs celecoxib and diclofenac. Furthermore, docking studies for our compounds within 15-LOX and COX-2 active sites revealed good agreement with the biological evaluations. The proposed compounds could be promising multi-targeted anti-inflammatory candidates to treat resistant inflammatory conditions.

Nematocidal and Bactericidal Activities of Green Synthesized Silver Nanoparticles Mediated by Ficus sycomorus Leaf Extract.

Nanoparticles effectively control most plant pathogens, although research has focused more on their antimicrobial than their nematocidal properties. This study synthesized silver nanoparticles (Ag-NPs) through a green biosynthesis method using an aqueous extract of Ficus sycomorus leaves (FS-Ag-NPs). The nanoparticles were characterized using SEM, TEM, EDX, zeta sizer, and FTIR. The TEM results showed that the synthesized NPs were nanoscale and had an average particle size of 33 ± 1 nm. The elemental silver signal at 3 keV confirmed the formation of Ag-NPs from an aqueous leaf extract of F. sycomorus. The FTIR analysis revealed the existence of several functional groups in the prepared Ag-NPs. The strong-broad band detected at 3430 cm-1 indicated the stretching vibration of -OH (hydroxyl) and -NH2 (amine) groups. The nematocidal activity of biosynthesized FS-Ag-NPs has been evaluated in vitro against the root-knot nematode Meloidogyne incognita at 24, 48, and 72 h. The FS-Ag-NPs at a 200 µg/mL concentration applied for 48 h showed the highest effectiveness, with 57.62% nematode mortality. Moreover, the biosynthesized FS-Ag-NPs were also tested for their antibacterial activity against Pectobacterium carotovorum, P. atrosepticum, and Ralstonia solanacearum. With the application of nanoparticles, the reduction in bacterial growth gradually increased. The most potent activity at all concentrations was found in R. solanacearum, with values of 14.00 ± 2.16, 17.33 ± 2.05, 19.00 ± 1.41, 24.00 ± 1.41, and 26.00 ± 2.83 at concentrations of 5, 10, 15, 20, and 25 µg/mL, respectively, when compared with the positive control (Amoxicillin 25 µg) with a value of 16.33 ± 0.94. At the same time, the nanoparticles showed the lowest reduction values against P. atrosepticum when compared to the control. This study is the first report on the nematocidal activity of Ag-NPs using F. sycomorus aqueous extract, which could be a recommended treatment for managing plant-parasitic nematodes due to its simplicity, stability, cost-effectiveness, and environmentally safe nature.

Triple targeting of mutant EGFRL858R/T790M, COX-2, and 15-LOX: design and synthesis of novel quinazolinone tethered phenyl urea derivatives for anti-inflammatory and anticancer evaluation.

We designed and synthesised novel quinazolinone tethered phenyl urea derivatives (6a-p) that triple target the double mutant EGFRL858R/T790M, COX-2, and 15-LOX. Compounds (6e, 6d, 6j, 6m, and 6n) not only had low micromolar IC50 inhibitory activities against the three targets, but they also showed good selectivity for COX-2 over COX-1 and for EGFRL858R/T790M over wild-type EGFR. Except for 6e and 6n, all of the tested compounds inhibited the NO production significantly more potently than celecoxib, diclofenac, and indomethacin. Compounds 6i and 6k reduced ROS levels more effectively than celecoxib and diclofenac. In terms of inhibiting TNF-α production, 6o-treated cells showed TNF-α level, which is ∼10 times lower than celecoxib. Furthermore, 6e and 6j had the highest anticancer activity against the breast cancer cell line BT-459 with growth inhibition percentages of 67.14 and 70.07%, respectively. Docking studies confirm their favoured binding affinity. The proposed compounds could be promising multi-targeted leads.

Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm.f. is widely used in various traditional systems of medicine worldwide. Since over 5000 years ago, several cultures have used A. vera extract medicinally for conditions ranging from diabetes to eczema. It has been shown to reduce the symptoms of diabetes by enhancing insulin secretion and protecting pancreatic islets. AIM OF THE WORK: This research study aimed to investigate the in-vitro antioxidant effect, the acute oral toxicity, and the possible pharmacological in-vivo anti-diabetic activity with histological examination of the pancreas of the standardized deep red A. vera flowers methanolic extracts (AVFME). MATERIALS AND METHODS: The liquid-liquid extraction procedure and TLC technique were used to investigate chemical composition. Total phenolics and flavonoids in AVFME were quantified by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. The present study involved evaluating the in-vitro antioxidant effect of AVFME using ascorbic acid as the reference standard, an acute oral toxicity study by using thirty-six albino rats and different concentrations of AVFME (200 mg/kg, 2, 4, 8 and 10 g/kg b.w.). Furthermore, the in-vivo anti-diabetic study was performed on alloxan-induced diabetes in rats (120 mg/kg, I.P.) and two doses of AVFME (200 and 500 mg/kg b.w., orally) were used as compared to glibenclamide (5 mg/kg, orally) as a standard hypoglycemic sulfonylurea medication. A histological examination of the pancreas was performed. RESULTS: AVFME resulted in the highest phenolic content of 150.44 ± 4.62 mg gallic acid equivalent per gram (GAE/g) along with flavonoid content of 70.38 ± 0.97 mg of quercetin equivalent per gram (QE/g). An in-vitro study revealed that the antioxidant effect of AVFME was strong as ascorbic acid. The results of the in-vivo studies showed that the AVFME didn't cause any apparent toxicity signs or death in all groups at different doses which proves the safety of this extract with a wide therapeutic index. The antidiabetic activity of AVFME demonstrated a considerable drop in blood glucose levels as glibenclamide, without severe hypoglycemia or significant weight gain which is considered an advantage of AVFME over glibenclamide use. The histopathological study of pancreatic tissues confirmed the protective effect of AVFME on the pancreatic beta-cells. The extract is proposed to have antidiabetic activity through inhibition of α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Molecular docking studies were conducted to understand possible molecular interactions with these enzymes. CONCLUSION: AVFME represents a promising alternative source of active constituents against diabetes mellitus (DM) based on its oral safety, antioxidant, anti-hyperglycemic activities, and pancreatic protective effects. These data revealed the antihyperglycemic activity of AVFME is mediated by pancreatic protective effects while significantly enhancing insulin secretion through increasing functioning beta cells. This suggests that AVFME has the potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes (T2DM).