In silico homology modeling of dengue virus non-structural 4B (NS4B) protein and its molecular docking studies using triterpenoids.

BACKGROUND: Dengue fever has become a significant worldwide health concern, because of its high morbidity rate and the potential for an increase in mortality rates due to lack of adequate treatment. There is an immediate need for the development of effective medication for dengue fever. METHODS: Homology modeling of dengue virus (DENV) non-structural 4B (NS4B) protein was performed by SWISS-MODEL to predict the 3D structure of the protein. Structure validation was conducted using PROSA, PROCHECK, Ramachandran plot, and VERIFY-3D. MOE software was used to find out the in-Silico inhibitory potential of the five triterpenoids against the DENV-NS4B protein. RESULTS: The SWISS-MODEL was employed to predict the three-dimensional protein structure of the NS4B protein. Through molecular docking, it was found that the chosen triterpenoid NS4B protein had a high binding affinity interaction. It was observed that the NS4B protein binding energy for 15-oxoursolic acid, betulinic acid, ursolic acid, lupeol, and 3-o-acetylursolic acid were - 7.18, - 7.02, - 5.71, - 6.67 and - 8.00 kcal/mol, respectively. CONCLUSIONS: NS4B protein could be a promising target which showed good interaction with tested triterpenoids which can be developed as a potential antiviral drug for controlling dengue virus pathogenesis by inhibiting viral replication. However, further investigations are necessary to validate and confirm their efficacy.

Synthesis biological evaluation and molecular docking of isatin hybrids as anti-cancer and anti-microbial agents.

Isatin, known as 1H-indole-2,3-dione, was originally recognised as a synthetic molecule until its discovery in the fruits of the cannonball tree, Couroupita guianensis. It is naturally occurring in plants of the genus Isatis and serves as a metabolic derivative of adrenaline in humans. Isatin possesses significant pharmacological importance, and its synthetic versatility has prompted extensive interest in its derivative compounds due to their diverse biological and pharmacological properties. These derivatives represent a valuable class of heterocyclic compounds with potential applications as precursors for synthesizing numerous valuable drugs. In the pursuit of advancing our research on isatin hybrids, we investigate the utilisation of readily available hydrazonoindolin-2-one and isatin as starting materials for the synthesis of a wide range of analogues. Characterisation of the synthesized compounds was carried out through various analytical techniques. Furthermore, the obtained compounds were subjected to extensive testing to evaluate their anticancer and antimicrobial activities. Specifically, their efficacy against key proteins, namely Staphylococcus aureus protein (PDB ID: 1JIJ), Escherichia coli protein (PDB ID: 1T9U), Pseudomonas aeruginosa protein (PDB ID: 2UV0), and Acinetobacter baumannii protein (PDB ID: 4HKG), was examined through molecular docking calculations. Several molecules, such as 3, 4, 6, 16, and 19, displayed remarkable activity against the renal cancer cell line UO-31. Additionally, the results of antimicrobial activity testing revealed that compound 16 exhibited significant cytotoxicity against Candida albicans and Cryptococcus neoformans. Subsequently, ADME/T calculations were performed to gain insights into the potential effects and reactions of these molecules within human metabolism. This comprehensive study provides valuable insights into the potential pharmacological applications of isatin derivatives and underscores their significance in drug development.

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Biological Properties of Mentha viridis L. Essential Oil and Its Main Monoterpene Constituents.

This research aimed to evaluate the antidiabetic, dermatoprotective, and antibacterial activities of Mentha viridis L. essential oil (MVEO) collected in the province of Ouezzane (Northwest Morocco). Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the main constituents of MVEO were carvone (37.26 %), 1,8-cineole (11.82 %), limonene (5.27 %), α-terpineol (4.16 %), and ß-caryophyllene (4.04 %). MVEO showed strong inhibitory effects on α-amylase and α-glucosidase activities, exceeding those of acarbose, but weak anti-elastase activity. The main compounds, ß-caryophyllene (IC50=79.91±2.24 and 62.08±2.78 µg/mL) and limonene (IC50=90.73±3.47 and 68.98±1, 60 µg/mL), demonstrated the strongest inhibitory effects on both digestive enzymes (α-glucosidase and α-amylase, respectively). In silico investigations, using molecular docking, also showed the inhibitory potential of these bioactive compounds against the enzymes tested. In conclusion, MVEO, due to its main components such as limonene, 1,8-cineole, ß-caryophyllene, carvone, and α-terpineol, shows promising prospects for drug discovery and natural therapeutic applications.

Degradation of Argan oils used in edible and cosmetic applications after exposure to UV light.

This study investigates for the first time the effects of UV light exposure on the chemical composition of artisanal and cold-pressed culinary and cosmetic argan oils, as well as their quality and biological activities. We ascertained the oxidative stability of both types of oil through measurements of the peroxide value, acidity, UV-spectrophotometric indexes (E232 and E270), and iodine value. Over the course of eight hours at room temperature, the impact of UV light on the breakdown of tocopherols, polyphenols, chlorophylls, and carotenoid pigments was examined. The findings showed that during photo-oxidation, acidity, peroxide value, and particular extinction coefficients (E232 and E270) gradually increased. On the other hand, a decline in the content of polyphenols, tocopherols, carotenoid, and chlorophyll was noted. Interestingly, iodine levels failed to improve. Although after an eight-hour degradation, the physicochemical profile of argan oils remained exceptional. DPPH• (1,1-Diphenyl-2-picrylhydrazyl) antioxidant activity tests showed a gradual decrease in radical inhibition over time, which was attributed to lower levels of tocopherol and polyphenol. However, roasted oils showed antifungal action against Botrytis cinerea fungus, while Argan vegetable oils showed no activity against Escherichia coli, Microbacterium resistens, Staphylococcus saprophyticus, and Raoultella ornithinolytica, according to antimicrobial assays.

Phytochemical-mediated regulation of aflatoxigenic fungi contamination in a shifting climate and environment.

Mycotoxin contamination poses a significant problem in developing countries, particularly in northern Pakistan's fluctuating climate. This study aimed to assess aflatoxin contamination in medicinal and condiment plants in Upper Dir (dry-temperate) and Upper Swat (moist-temperate) districts. Plant samples were collected and screened for mycotoxins (Aflatoxin-B1 and Aflatoxin-B-2). Results showed high levels of AFB-1 (11,505.42 ± 188.82) as compared to AFB-2 (846 ± 241.56). The maximum contamination of AFB-1 in Coriandrum sativum (1154.5 ± 13.43 ng to 3328 ± 9.9 ng) followed by F. vulgare (883 ± 9.89 ng to 2483 ± 8.4 ng), T. ammi (815 ± 11.31 ng to 2316 ± 7.1 ng), and C. longa (935.5 ± 2.12 ng to 2009 ± 4.2 ng) while the minimum was reported in C. cyminum (671 ± 9.91 ng to 1995 ± 5.7 ng). Antifungal tests indicated potential resistance in certain plant species (C. cyminum) while A. flavus as the most toxins contributing species due to high resistance below 80% (54.2 ± 0.55 to 79.5 ± 2.02). HPLC analysis revealed hydroxyl benzoic acid (5136 amu) as the dominant average phytochemical followed by phloroglucinol (4144.31 amu) with individual contribution of 8542.08 amu and 12,181.5 amu from C. cyaminum. The comparison of average phytochemicals revealed the maximum concentration in C. cyminum (2885.95) followed by C. longa (1892.73). The findings revealed a statistically significant and robust negative correlation (y = - 2.7239 × + 5141.9; r = - 0.8136; p < 0.05) between average mycotoxins and phytochemical concentrations. Temperature positively correlated with aflatoxin levels (p < 0.01), while humidity had a weaker correlation. Elevation showed a negative correlation (p < 0.05), while geographical factors (latitude and longitude) had mixed correlations (p < 0.05). Specific regions exhibited increasing aflatoxin trends due to climatic and geographic factors.

Isolation of a novel isoprenylated phenolic compound and neuroprotective evaluation of Dodonaea viscosa extract against cerebral ischaemia-reperfusion injury in rats.

Dodonaea viscosa grows widely in Saudi Arabia, but studies evaluating its neuroprotective activity are lacking. Thus, this study aimed to isolate and identify the secondary metabolites and evaluate the neuroprotective effects of D. viscosa leaves. The isolation and identification of phytochemicals were performed using chromatographic and spectroscopic techniques. The neuroprotective potential of the extract was evaluated against focal cerebral ischaemia-reperfusion injury in rat model. Neurobehavioural deficits in the rats were evaluated, and their brains were harvested to measure infarct volume and oxidative biomarkers. Results revealed the presence of three compounds: a novel isoprenylated phenolic derivative that was elucidated as 4-hydroxy-3-(3'-methyl-2'-butenyl) phenyl 1-O-ß-D-apiosyl-(1''' â†’ 6'')- ß-D-glucopyranoside (named Viscomarfadol) and two known compounds (isorhamnetin-3-O-rutinoside and epicatechin (4-8) catechin). Pre-treatment of the rats with the extract improved neurological outcomes. It significantly reduced neurological deficits and infarct volume; significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels; and significantly elevated antioxidant (superoxide dismutase, catalase, and glutathione) activities. These results indicate that D. viscosa is a promising source of bioactive compounds that can improve neurological status, decrease infarct volume, and enhance antioxidant activities in rats with cerebral ischaemic injury. Thus, D. viscosa could be developed into an adjuvant therapy for ischaemic stroke and other oxidative stress-related neurodegenerative disorders. Further investigations are warranted to explore other bioactive compounds in D. viscosa and evaluate their potential neuroprotective activities.

Microsatellite-based diversity analysis and the development of core-set germplasm in Pakistani barley lines.

Illustrating the population structure and genetic diversity in selected germplasm resources (after three year multi locations trials) plays a key role which directly utilize the selection of lines in a population for accumulative trait breeding in crops. In order to further understand, the structure of population and genetic variability, we explored 100 selected lines, cultivated for three consecutive years (2016-2019) in swat, University of Malakand, Khyber Pakhtunkhwa Pakistan and Provinces of China (Chongqing and Beijing) with 33 mapped SSR markers. The integrated population structure analysis in a core of hundred germplasm with Pakistani origin with three approved commercial barley cultivars have strong stratification that allowed their division into four major subpopulations (i.e. PI, PII, PIII and PIV) and an admixture subpopulation, with 52, 9, 15 and 27 germplasm respectively. A total of 133 alleles were identified with mean value of 0.80 Polymorphic information content. The number of alleles detected by the system varied from two alleles amplified to as six with an average of 4.03 per SSR marker pair. The gene diversity ranged from 0.56 to 0.98 with an average of 0.82 in selected germplasm resources. Based on the SSR data, the 100 selected germplasm with three cultivars were classified into four main phylogenetic Linages (LI, LII, LIII and LIV) which corresponded to the phylogenic grouping in genotypes. We assembled a core set of 20 barley genotypes (~1/5 of original population size) to sustain sufficient mapping of SSR marker with Phenotype, in which we proposed four SSR markers, Bmac0040, Bmac0134, Bmag0125 and Bmag0211 for malt gene and marker (Bmac0399) for tolerance to salinity gene, which will be applicable for marker assisted breeding in barley gene resources.

Synthesis and Characterization of MIPs for Selective Removal of Textile Dye Acid Black-234 from Wastewater Sample.

Herein, a molecularly imprinted polymer (MIP) was prepared using bulk polymerization and applied to wastewater to aid the adsorption of targeted template molecules using ethylene glycol dimethacrylate (EGDMA), methacrylic acid (MAA), acid black-234 (AB-234), 2,2'-azobisisobutyronitrile (AIBN), and methanol as a cross linker, functional monomer, template, initiator, and porogenic solvent, respectively. For a non-molecularly imprinted polymer (NIP), the same procedure was followed but without adding a template. Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a surface area analyzer were used to determine the surface functional groups, morphology and specific surface area of the MIP and NIP. At pH 5, the AB-234 adsorption capability of the MIP was higher (94%) than the NIP (31%). The adsorption isotherm data of the MIP correlated very well with the Langmuir adsorption model with Qm 82, 83 and 100 mg/g at 283 K, 298 K, and 313 K, respectively. The adsorption process followed pseudo-second-order kinetics. The imprinted factor (IF) and Kd value of the MIP were 5.13 and 0.53, respectively. Thermodynamic studies show that AB-234 dye adsorption on the MIP and NIP was spontaneous and endothermic. The MIP proved to be the best selective adsorbent for AB-234, even in the presence of dyes with similar and different structures than the NIP.

Rapid Detection of Cd2+ Ions in the Aqueous Medium Using a Highly Sensitive and Selective Turn-On Fluorescent Chemosensor.

Herein, a novel optical chemosensor, (CM1 = 2, 6-di((E)-benzylidene)-4-methylcyclohexan-1-one), was designed/synthesized and characterized by 1H-NMR and FT-IR spectroscopy. The experimental observations indicated that CM1 is an efficient and selective chemosensor towards Cd2+, even in the presence of other metal ions, such as Mn2+, Cu2+, Co2+, Ce3+, K+, Hg2+,, and Zn2+ in the aqueous medium. The newly synthesized chemosensor, CM1, showed a significant change in the fluorescence emission spectrum upon coordination with Cd2+. The formation of the Cd2+ complex with CM1 was confirmed from the fluorometric response. The 1:2 combination of Cd2+ with CM1 was found optimum for the desired optical properties, which was confirmed through fluorescent titration, Job's plot, and DFT calculation. Moreover, CM1 showed high sensitivity towards Cd2+ with a very low detection limit (19.25 nM). Additionally, the CM1 was recovered and recycled by the addition of EDTA solution that combines with Cd2+ ion and, hence, frees up the chemosensor.

One Pot Synthesis, Biological Efficacy of AuNPs and Au-Amoxicillin Conjugates Functionalized with Crude Flavonoids Extract of Micromeria biflora.

Amoxicillin is the most widely used antibiotic in human medicine for treating bacterial infections. However, in the present research, Micromeria biflora's flavonoids extract mediated gold nanoparticles (AuNPs) were conjugated with amoxicillin (Au-amoxi) to study their efficacy against the inflammation and pain caused by bacterial infections. The formation of AuNPs and Au-amoxi conjugates were confirmed by UV-visible surface plasmon peaks at 535 nm and 545 nm, respectively. The scanning electron microscopy (SEM), zeta potential (ZP), and X-ray diffraction (XRD) studies reveal that the size of AuNPs and Au-amoxi are found to be 42 nm and 45 nm, respectively. Fourier-transform infrared spectroscopy (FT-IR) absorption bands at 3200 cm-1, 1000 cm-1, 1500 cm-1, and 1650 cm-1 reveal the possible involvement of different moieties for the formation of AuNPs and Au-amoxi. The pH studies show that AuNPs and Au-amoxi conjugates are stable at lower pH. The carrageenan-induced paw edema test, writhing test, and hot plate test were used to conduct in vivo anti-inflammatory and antinociceptive studies, respectively. According to in vivo anti-inflammatory activity, Au-amoxi compounds have higher efficiency (70%) after 3 h at a dose of 10 mg/kg body weight as compared to standard diclofenac (60%) at 20 mg/kg, amoxicillin (30%) at 100 mg/kg, and flavonoids extract (35%) at 100 mg/kg. Similarly, for antinociceptive activities, writhing test results show that Au-amoxi conjugates produced the same number of writhes (15) but at a lower dose (10 mg/kg) compared to standard diclofenac (20 mg/kg). The hot plate test results demonstrate that the Au-amoxi has a better latency time of 25 s at 10 mg/kg dose when compared to standard Tramadol of 22 s at 30 mg/ kg, amoxicillin of 14 s at 100 mg/kg, and extract of 14 s at 100 mg/kg after placing the mice on the hot plate for 30, 60, and 90 min with a significance of (p ≤ 0.001). These findings show that the conjugation of AuNPs with amoxicillin to form Au-amoxi can boost its anti-inflammatory and antinociceptive potential caused by bacterial infections.

Thiosemicarbazide binds with the dicopper center in the competitive inhibition of mushroom tyrosinase enzyme: Synthesis and molecular modeling of theophylline analogues.

Theophylline is long known for its anti-ageing and anti-oxidative properties. Moreover, Tyrosinase is a crucial enzyme that regulates the melanin synthetic pathway, which is involved in various physiological metabolic processes including aging. The current paper describes the synthesis of various heterocyclic systems coupled with theophylline moiety along with their tyrosinase inhibition activity in view to identify the potent nucleus. Around 19 compounds were synthesized and screened for enzyme inhibition. Based on the current study, it is suggested that compound 18 having thiosemicarbazide has strong enzyme inhibition potential. The enzyme kinetics and docking studies provide important insights into how the compound interacts with the mushroom tyrosinase active site. The work will provide clue to developing new, potent tyrosinase inhibitors for drug development.

Management of plantar heel pain: a best practice guide informed by a systematic review, expert clinical reasoning and patient values.

OBJECTIVE: To develop a best practice guide for managing people with plantar heel pain (PHP). METHODS: Mixed-methods design including systematic review, expert interviews and patient survey. DATA SOURCES: Medline, Embase, CINAHL, SPORTDiscus, Cochrane Central Register of Controlled Trials, trial registries, reference lists and citation tracking. Semi-structured interviews with world experts and a patient survey. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) evaluating any intervention for people with PHP in any language were included subject to strict quality criteria. Trials with a sample size greater than n=38 were considered for proof of efficacy. International experts were interviewed using a semi-structured approach and people with PHP were surveyed online. RESULTS: Fifty-one eligible trials enrolled 4351 participants, with 9 RCTs suitable to determine proof of efficacy for 10 interventions. Forty people with PHP completed the online survey and 14 experts were interviewed resulting in 7 themes and 38 subthemes. There was good agreement between the systematic review findings and interview data about taping (SMD: 0.47, 95% CI 0.05 to 0.88) and plantar fascia stretching (SMD: 1.21, 95% CI 0.78 to 1.63) for first step pain in the short term. Clinical reasoning advocated combining these interventions with education and footwear advice as the core self-management approach. There was good expert agreement with systematic review findings recommending stepped care management with focused shockwave for first step pain in the short-term (OR: 1.89, 95% CI 1.18 to 3.04), medium-term (SMD 1.31, 95% CI 0.61 to 2.01) and long-term (SMD 1.67, 95% CI 0.88 to 2.45) and radial shockwave for first step pain in the short term (OR: 1.66, 95% CI 1.00 to 2.76) and long term (OR: 1.78, 95% CI 1.07 to 2.96). We found good agreement to 'step care' using custom foot orthoses for general pain in the short term (SMD: 0.41, 95% CI 0.07 to 0.74) and medium term (SMD: 0.55, 95% CI 0.09 to 1.02). CONCLUSION: Best practice from a mixed-methods study synthesising systematic review with expert opinion and patient feedback suggests core treatment for people with PHP should include taping, stretching and individualised education. Patients who do not optimally improve may be offered shockwave therapy, followed by custom orthoses.

Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins.

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

Phyto-Extract-Mediated Synthesis of Silver Nanoparticles Using Aqueous Extract of Sanvitalia procumbens, and Characterization, Optimization and Photocatalytic Degradation of Azo Dyes Orange G and Direct Blue-15.

Green synthesis of silver nanoparticles (AgNPs) employing an aqueous plant extract has emerged as a viable eco-friendly method. The aim of the study was to synthesize AgNPs by using plant extract of Sanvitalia procumbens (creeping zinnia) in which the phytochemicals present in plant extract act as a stabilizing and reducing agent. For the stability of the synthesized AgNPs, different parameters like AgNO3 concentration, volume ratios of AgNO3, temperature, pH, and contact time were studied. Further, AgNPs were characterized by UV-visible spectroscopy, FT-IR (Fourier Transform Infrared Spectroscopy), XRD (X-ray Diffraction), SEM (Scanning Electron Microscopy), and EDX (Energy Dispersive X-ray Spectrometer) analysis. FT-IR analysis showed that the plant extract contained essential functional groups like O-H stretching of carboxylic acid, N-H stretching of secondary amides, and C-N stretching of aromatic amines, and C-O indicates the vibration of alcohol, ester, and carboxylic acid that facilitated in the green synthesis of AgNPs. The crystalline nature of synthesized AgNPs was confirmed by XRD, while the elemental composition of AgNPs was detected by energy dispersive X-ray analysis (EDX). SEM studies showed the mean particle diameter of silver nanoparticles. The synthesized AgNPs were used for photocatalytic degradation of Orange G and Direct blue-15 (OG and DB-15), which were analyzed by UV-visible spectroscopy. Maximum degradation percentage of OG and DB-15 azo dyes was observed, without any significant silver leaching, thereby signifying notable photocatalytic properties of AgNPs.

Caralluma europaea (Guss.) N.E.Br.: Anti-Inflammatory, Antifungal, and Antibacterial Activities against Nosocomial Antibiotic-Resistant Microbes of Chemically Characterized Fractions.

Caralluma europaea (Guss.) N.E.Br.: (C. europaea) is a wild medicinal plant belonging to the family Apocynaceae. It is commonly used in traditional medicines for treating several diseases. The present work aims to evaluate the anti-inflammatory, antibacterial, and antifungal potentials of C. europaea fractions including hydro ethanol (ET CE), n-butanol (But CE), and polyphenol (Poly CE). The chemical composition of hydroethanol, n-butanol, and polyphenol-rich fractions from C. europaea were determined using GC-MS after silylation. The anti-inflammatory effect of hydroethanol, n-butanol, and polyphenol-rich fractions was studied by carrageenan-induced paw edema. Antibacterial and antifungal activities of hydroethanol, n-butanol, and polyphenol-rich fractions against Gram-positive bacteria, Gram-negative bacteria, and yeasts were assessed using the disc diffusion and micro-dilution assays. The findings of the chemical characterization affirmed the presence of interesting bioactive compounds in C. europaea fractions. The polyphenol-rich fraction was the best inhibitor of edema by75.68% after 6 h of treatment. The hydroethanol fraction was the most active against both bacteria and yeasts. This study contributes to society as it provides potential bioactive compounds in C. europaea extract, which may help in fighting nosocomial antibiotic-resistant microbes.

Combined pretreatment of sugarcane bagasse using alkali and ionic liquid to increase hemicellulose content and xylanase production.

BACKGROUND: Lignin in sugarcane bagasse (SB) hinders its utilization by microorganism, therefore, pretreatment methods are employed to make fermentable components accessible to the microbes. Multivariate analysis of different chemical pretreatment methods can aid to select the most appropriate strategy to valorize a particular biomass. RESULTS: Amongst methods tested, the pretreatment by using sodium hydroxide in combination with methyltrioctylammonium chloride, an ionic liquid, (NaOH+IL) was the most significant for xylanase production by Bacillus aestuarii UE25. Investigation of optimal levels of five significant variables by adopting Box-Behnken design (BBD) predicted 20 IU mL- 1 of xylanase and experimentally, a titer of 17.77 IU mL- 1 was obtained which indicated the validity of the model. The production kinetics showed that volumetric productivity of xylanase was much higher after 24 h (833.33 IU L- 1 h- 1) than after 48 h (567.08 IU L- 1 h- 1). The extracted xylan from SB induced more xylanase in the fermentation medium than pretreated SB or commercially purified xylan. Nuclear Magnetic Resonance, Fourier transform infrared spectroscopy and scanning electron microscopy of SB indicated removal of lignin and changes in the structure of SB after NaOH+IL pretreatment and fermentation. CONCLUSION: Combined pretreatment of SB with alkali and methyltrioctylammonium chloride appeared better than other chemical methods for bacterial xylanase production and for the extraction of xylan form SB.

Analysis of a "3-(Naphthalen-1-ylimino) Indoline-2-one" compound and Its Antimicrobial Assessment Using Lipid-based Self-nanoemulsifying Formulations.

In recent years, indole derivatives have acquired conspicuous significance due to their wide spectrum of biological activities-antibacterial, antiviral, and anticonvulsant. This compound is derived from naturally grown plants. Therefore, synthesis of a novel "3-(Naphthalen-1-ylimino) indoline-2-one" compound (2) and its analysis using UPLC systems along with antimicrobial assessment was the aim of the current study. Isatin was used as a parent drug for synthesizing compound (2). Liquid Chromatographic analysis was performed using a C18 BEH column (1.7 µm 2.1 × 50 mm) by UPLC systems. Degradation studies were carried out to see whether acid, base, thermal, and oxidizing agents had any impact on the synthesized molecule in stress conditions (100 °C). A lipid-based self-nanoemulsifying formulation was developed and selectivity, specificity, recovery, accuracy, and precision were measured as part of the UPLC system's validation process. Antimicrobial studies were conducted using gram-positive and gram-negative bacteria. The standard samples were run with a concentration range of 5.0-100.0 µg/mL using the isocratic mobile phase comprising of methanol/water (70/30 %v/v) at 234 nm; good linearity (R2 = 0.9998) was found. The lower limits of detection (LOD) and quantitation (LOQ) of the method were found to be 0.81 µg/mL and 2.5 µg/mL, respectively. The coefficients of variation were found to be less than 2%. The antimicrobial study suggests that compound (2) has a substantial growth effect against gram-negative bacteria. It was successfully synthesized and applied to measure the concentrations in lipid-based dosage form, along with potent antimicrobial activities.

Synthesis and Evaluation of New Coumarin Derivatives as Antioxidant, Antimicrobial, and Anti-Inflammatory Agents.

New pyranocoumarin and coumarin-sulfonamide derivatives were prepared and evaluated for their antioxidant, antimicrobial, and/or anti-inflammatory activities. Coumarin-sulfonamide compounds 8a-d demonstrated significant antioxidant activity, while 7c,d, 8c,d, and 9c,d exhibited antimicrobial activity equal to or higher than the standard antimicrobials against at least one tested microorganism. Regarding the anti-inflammatory testing, pyranocoumarins 2b, 3a,b and 5c and coumarin-sulfonamide compound 9a showed more potent antiproteinase activity than aspirin in vitro; however, five compounds were as potent as aspirin. The anti-inflammatory activity of the promising compounds was further assessed pharmacologically on formaldehyde-induced rat paw oedema and showed significant inhibition of oedema. For in vitro COX-inhibitory activity of coumarin derivatives, pyranocoumarin derivative 5a was the most selective (SI = 152) and coumarin-sulfonamide derivative 8d was most active toward COX-2 isozyme. The most active derivatives met the in silico criteria for orally active drugs; thus, they may serve as promising candidates to develop more potent and highly efficient antioxidant, antimicrobial, and/or anti-inflammatory agents.

Phytochemical Identification, Acute, and Sub-Acute Oral Toxicity Studies of the Foliar Extract of Withania frutescens.

Withania frutescens (W. frutescens) is a medicinal plant widely used to treat several diseases. This work aims to study phytochemical composition as well as acute and subacute toxicity of W. frutescens hydroethanolic extract in mice. The phytochemical composition of W. frutescens extract was performed using gas chromatographic analysis. Acute toxicity was studied in vivo with oral administration of single doses 400 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was studied with the administration of repeated doses of 400 mg/kg/day and 2000 mg/kg/day for 28 days. Phytochemical analysis of W. frutescens hydro-ethanolic extract confirmed the presence of interesting chemical compounds. Acute toxicity results showed no toxic symptoms in mice treated with an increasing dose up to a maximum of 2000 mg/kg. Alongside acute toxicity, subacute data showed no clinical symptoms nor biochemical or histological alteration in mice treated with an increasing dose up to a maximum of 2000 mg/kg compared to the control group (p < 0.05). This study shows no toxic effects in animals treated with W. frutescens extract, and, therefore, this plant can be considered safe in animals up to 2000 mg/kg under both acute and subacute toxicity conditions.