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The HslVU enzyme complex, a proteasomal analog found in bacteria, consists of two components, i.e., the HslV protease and the HslU ATPase. These proteins come together to form a functional enzyme complex, where the C-terminal helix of each HslU subunit is inserted into the binding pocket of each HslV dimer. This interaction leads to the activation of the HslV protease through allosteric mechanisms, enabling its enzymatic function. This bacterial complex is reflected as an attractive target for drug development due to its presence in disease-causing microorganisms and concurrent absence in humans. The objective of this research was to identify certain promising drug candidates that could excessively stimulate the HslV protease, leading to uncontrolled protein breakdown in the pathogens. Four dihydropyrimidone derivatives have been identified as potential activators of HslV protease exhibiting high docking scores, favorable binding patterns, and significant in vitro activation capabilities. These compounds have demonstrated effective dose 50 values within the sub-micromolar range, i.e., 0.4–0.58 µM. Normal mode analysis investigations provided additional confirmation regarding the stability of the conformational interactions between the HslV protease and the active compounds. In addition, the predicted absorption, distribution, metabolism, excretion, and toxicity properties of these lead compounds remarkably demonstrated their considerable drug-like and non-toxic qualities. This study not only presents more potent small non-peptide activators of the HslV protease but also enhances the understanding regarding the mechanism of HslVU complex activation via small non-peptidic molecules.

Citronellyl acetate is a crucial component of flavor and fragrance in the food, cosmetic, and pharmaceutical sectors. In non-aqueous media, it can be successfully produced via lipase catalysis. This study focuses on the lipase-catalyzed trans-esterification of citronellol alcohol with geranyl acetate ester in a non-aqueous medium to produce citronellyl acetate. For the synthesis of citronellyl acetate, crude acetone powders isolated from several plant seedlings of black cumin, fenugreek, coriander, flax, and rape seed were examined for lipase activity. Black cumin seedling lipase had the highest level of citronella acetate production with a yield of 76.32% in 72 h of reaction time. To assess the impact of different reaction parameters on citronellyl acetate production in organic solvents, hexane was chosen as the best solvent, and black cumin seedling lipase was selected as the best biocatalyst. The highest conversion yield of ester (76.32%) was found when 0.25 M of geraniol acetate and 0.25 M of citronellol reacted at 41 oC after 72 h in the presence of 0.25 g of seedling lipase enzyme in n-hexane. It has been determined that crude black cumin seedling lipase is inexpensive yet effective and has the potential to be used industrially for the synthesis of terpene esters.

The purpose of this research was to examine the interaction between metabolites of Lactobacillus plantarum YW11, characterized through GC–mass spectra (MS) analysis, and the FN1 protein in cases of familial pulmonary fibrosis, found from hub genes analysis. GC–MS analysis was performed to identify metabolites in L. plantarum. Then, gene expression analysis and functional annotations were conducted to investigate the hub genes. A network of hub genes and transcription factors (TFs) was constructed, highlighting the significance of FN1 in the disease’s etiology. Molecular docking was employed to explore the interaction between the characterized metabolites and the FN1 protein. Toxicity analysis was also carried out. Thirty-two active compounds of L. plantarum YW11 were characterized by GC–MS. The gene expression analysis identified 295 differentially expressed genes, including 10 hub genes and 6 TFs, providing further support for the involvement of FN1 protein in the disease. The results of the molecular docking studies suggest the therapeutic potential of targeting FN1, with the best docking result observed for the interaction between FN1 and the 2,4-di-tert-butylphenol metabolite (energy of −6.9 kcal/mol). The toxicity analysis and molecular dynamic simulations support the suitability of 2,4-di-tert-butylphenol as a candidate for targeting FN1.

Butea monosperma is a deciduous tree, widely distributed throughout India, Burma, and Ceylon. The present study was intended to investigate the anti-inflammatory effects of Butea monosperma on the induced inflammatory model by evaluating pro-inflammatory biomarkers and their computational analysis. The anti-inflammatory activity may be attributed to the phyto-constituents for inhibitory effects on the two pro-inflammatory mediators (IL-8 and TNF-α). For this purpose, rats (n = 48) were equally divided in each group, i.e., 8 each in the negative and positive control and 32 in the experimental group with 8 rats for each dose, i.e., 50, 100, 200, and 400 mg/kg. TNF-α and IL-8 were tested by serum enzyme-linked immunosorbent assay (ELISA). The ELISA results showed 400 mg/kg dose as the potent anti-inflammatory. The binding sites of target proteins (TNF-α and IL-8) were docked with the active compounds (butrin and butein) of Butea monosperma. The butrin (target: TNF-α) and butein (target: IL-8) showed −8.4 and −6.0 kcal/mol binding energies, respectively, compared to the (diclofenac) standard drug with −6.8 kcal/mol binding energy. Hence, we concluded that Butea monosperma can be subjected to as a useful anti-inflammatory drug.

In the current era, a potent drug is still needed on the market for the treatment of various diseases worldwide. Researchers mainly focus on those enzymes that cause these diseases. One of the major diseases is caused by an enzyme called urease, which increases the concentration of ammonia in the body upon hydrolysis. Researchers across the globe have keen interest to synthesize the potent inhibitor for this conversion. From this perspective, hybrid analogs of imidazopyridine and oxadiazole (1–20) were designed and efficiently synthesized followed by characterizing them through varied spectroscopic methods (1HNMR, 13CNMR, and HREI-MS). In addition, in vitro analyses of the synthesized compounds were conducted to evaluate their anti-urease potency. There was significant potential in most compounds analyzed, but analogs 15, 16, and 17 (IC50 = 2.20 ± 0.10 μM, IC50 = 2.50 ± 0.10 μM, and IC50 = 2.30 ± 2.10 μM, respectively) performed exceptionally well in comparison with thiourea (IC50 = 22.30 ± 0.44 μM). The selected candidates were further investigated under a molecular docking study to confirm protein ligand interactions. In addition, energy gap (E gap) of the HOMO–LUMO was explored via density functional theory studies.

The present study highlights the true potential of Rhizopus oligosporus IIB-08 to produce lipase enzyme under solid-state fermentation and focuses on improving the properties of lipase by immobilizing it on biogenic aluminium oxide nanoparticles (Al-NPs) for better resolution of active homochiral 2-octanol. For this purpose, almond meal substrate showed 10.44 ± 0.36 U·g−1 lipase activity. The immobilization of lipase on biogenic Al-NPs prepared using Mentha spicata leaf extract led towards improved stability and catalytic efficiency, resulting in a 9.3% increase in activity compared to free enzyme. This study also examined the potential of the immobilized lipase in the effective resolution of 2-octanol. Gas chromatography-mass spectrometry confirmed the presence of lipase-catalysed fatty acids, such as linolenic acid (C18:3), linoleic acid (C18:2), palmitic acid, and oleic acid (C18:1), with palmitic acid exhibiting the highest concentration (142 μg·ml−1) at a retention time of 23.2 min. This study concludes that R. oligosporus IIB-08 is a promising source for lipase production and demonstrates the significant potential of nanoparticle-immobilized lipase in resolving pharmaceutically important organic chemicals, thereby making it a promising approach for different industrial applications. However, further scaling up is needed for better implementation in the industry.

The current study aimed to analyze the stabilization of sunflower oil using white mustard (Brassica hirta) leaf extracts as well as their antioxidant potential and cytotoxicity. Selected plant leaves were macerated in different solvents such as n-hexane, chloroform, ethyl acetate, n-butanol, and methanol. The total flavonoid contents, total phenolic contents, the antioxidant activity by DPPH assay, and the inhibition of linoleic acid oxidation were also examined. Moreover, the stabilization of sunflower oil was evaluated by calculating the conjugated dienes, conjugated trienes, peroxide value, p-ansidine, and free fatty acid values. The cytotoxicity study in terms of the hemolytic activity of B. hirta leaf extract was evaluated and the maximum percentage of lysis was found to be safe (less than 5%). The results of the present study revealed that among others, methanolic white mustard (B. hirta) leaf extract possessed higher antioxidant potential and might be safely employed for the stabilization of vegetable oils.

Silver nanoparticles have special plasmonic and antibacterial characteristics that make them efficient in a variety of commercial medical applications. According to recent research, chemically synthesized silver nanoparticles are harmful even in low concentrations. It was crucial to identify appropriate synthesis methods that may have low costs and be nontoxic to the environment. Zingiber officinale (ginger) extracts used to prepare silver nanoparticles were inexpensive and environmentally friendly, and the best physicochemical characteristics were analyzed. Silver nanoparticles were characterized by using UV-visible spectroscopy, Scanning electron microscopy (SEM), and X-ray diffraction (XRD). The surface Plasmon resonance peak at 425 nm was observed using UV-Visible spectroscopy. Scanning electron microscopy observed that the nanoparticles were spherical and ranged in size from 5 to 35 nm. The XRD pattern values of 2θ: 38.2o, 46.3o, and 64.58o are used to determine the planes (111), (200), and (220). The silver nanoparticle’s existence was verified by the face-centered cubic (FCC). Silver nanoparticles were found to have antibacterial efficacy against gram-positive Staphylococcus and gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella Aerogenes, Salmonella, Staphylococcus and Escherichia coli. The antibacterial activity of silver nanoparticles was observed using the agar well diffusion (AWD) method at three different concentrations (100 μg/ml, 75 μg/ml, and 50 μg/ml). The zone of inhibition measured against the bacterial strains pseudomonas Aeruginosa, Klebsiella aerogenes, Escherichia coli, Salmonella and Staphylococcus which were (18.4±1.25 mm, 16.9±0.74 mm, 14.8±1.25 mm), (16.8±0.96 mm, 14.6±0.76 mm, 14.0±1.15 mm), (19.7±0.76 mm, 18.2±0.66 mm, 15.4±1.15 mm), (16.6±0.67 mm, 14.2±0.23 mm, 12.8±0.78 mm) and (12±0.68 mm, 10±0.20 mm, 08±0.15 mm). These nanoparticles’ potent antibacterial properties may enable them to be employed as nanomedicines for a variety of gram-negative bacterial illness treatments.

The present study was aimed to identify the indigenous fungal strains which could possibly be applied to the biore-mediation of heavy metal-contaminated soil. The contaminated soil samples of Korangi Industrial Estate Karachi were found to have total concentration of Cu 1.044 mgL1, and Pb 0.631 mgL–1. A total of eight indigenous strains of the fungus were isolated and screened for bioremediation capacity from heavy metals-contaminated soil. For the bioremediation of Lead (Pb) these same indigenous eight fungal strains were used for biological remediation. All the fungal isolated with enhanced bioremediation capability were through phenotypic and genotypical characterization. The topology of the phylograms established that the fungal isolates used in this study were allocated to: K1 (Penicillium notatum), K2 (Aspergillus parasiticus), K3 (Aspergillus fumigatus), K4 (Aspergillus flavus), K5 (Aspergillus terries), K6 (Fusarium solani), K7 (Penicillium chrysogenum), K8 (Aspergillus niger), K9 (Penicillium piceum) and K10 (Penicillium restrictum). Thus, K8 fungal isolate was found to be more efficient with maximum bioremediation capacity, for copper and lead removal efficiency, and selected for FTIR and SEM to find out the uptake of Cu and Pb which of the functional groups are involved, and further to detect the effects of bioleaching of both heavy metals on to the surface of K8 fungus biomass. The current study indicates that indigenous fungal isolates could be used with high potency to remediate or clean up the heavy metals-contaminated soil either by the technique of in situ or ex-situ bioremediation.

The widespread use of antibiotics has resulted in the emergence of multidrug-resistant bacteria. Therefore, it is essential to explore alternative strategies to effectively combat medically significant resistant pathogens. In recent years, nanoparticles (NPs) have emerged as a promising alternative source of antimicrobial agents. While nanoscale particles were traditionally synthesized using chemical techniques, the development of metallic NPs using biological methods has garnered attention. This current study focuses on the synthesis of iron NPs (Fe NPs) using metal-tolerant fungal strains, as numerous microorganisms serve as environmentally safe and durable precursors to produce persistent and bi-functional NPs. The study involved the isolation and evaluation of ten fungal strains that are resistant to heavy metals to determine their ability to produce Fe NPs. The biologically synthesized Fe NPs were characterized using X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and scanning electron microscopy techniques. The XRD results indicated the presence of Fe in nanopowder form, displaying a series of reflection angles (2θ) at 65° and 75° indicating the existence of cubic planes. EDX analysis revealed the presence of ferrous and ferric elements, along with zero-valent Fe NPs. Micrographs of the surface topology displayed spherical aggregation of the synthesized NPs. Furthermore, the Fe NPs exhibited promising antibacterial potential against selected bacterial strains, including Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Cronobacter sakazakii, Listeria innocua, and Enterococcus fecalis. This study demonstrates that the biological synthesis of metallic NPs is environmentally safe, and Fe NPs produced through mycological means could be utilized to combat antibiotic-resistant pathogenic strains.

Pseudomonas aeruginosa causes many infections worldwide. Multidrug-resistant bacteria are mostly watched in hospital-acquired infections and are linked with high mortality rates. This study aims to find a possible cure for P. aeruginosa by using an additive and synergistic combination of drugs. The Carbapenem-resistant P. aeruginosa were isolated and identified by using clinical and laboratory standards institute protocols and their antibiotic susceptibility testing was performed by using disc and well diffusion method. In computational analysis, all of the ligands and proteins were selected and docking was done using PYRX. Hundred samples were taken of isolated Gram-negative bacteria of which 25% were P. aeruginosa. Additive combinations (meropenem [MPM] + tobramycin [TOB] was 100% sensitive and imipenem + TOB was also 100% sensitive) and synergistic combinations (MPM + ciprofloxacin were 90% sensitive and amikacin and imipenem) were 100% sensitive according to CLSI protocol. In computational analysis, TOB gave the highest binding energy of −11.4, whereas MPM shows a binding energy of −9.3. In conclusion, Additive and synergistic combination of drugs showed good antibacterial activity against Pseudomonas aeruginosa. Hence it can be used as a good treatment option for P. aeruginosa.

The present study aimed to prepare hydrogel based on polyvinyl alcohol (PVA) and gelatin (Ge) and characterization of PVA/Ge hydrogel for their potential use as a sustained drug delivery system. Polyvinyl Alcohol (PVA) and-Gelatin (Ge) were cross-linked using glutaraldehyde (GA) as a crosslinking agent and hydrochloric acid (HCl) as a catalyst. Different feed polymer ratio and crosslinking agent concentration were used to prepare a series of PVA/Ge hydrogels. The obtained PVA/Ge hydrogels were investigated for dynamic and equilibrium swelling studies. The effect of polymers ratio, degree of crosslinking and pH of the medium on swelling of PVA/Ge hydrogels was investigated. Furthermore, the values of diffusion coefficient (D), volume fraction, polymer-solvent interaction parameter, molecular weight between crosslink and crosslink density were calculated. For swelling studies, 0.05M USP phosphate buffer solutions of different pH (1.2, 5.5, 6.5 and 7.5) were used. For the drug release study, ciprofloxacin HCl was loaded into selected samples as a model drug. The release of drug from these samples was performed for 12 hours in USP phosphate buffers of pH 1.2, 5.5 and 7.5. The release data from these samples were fitted into various kinetic models like zero order, first order, Higuchi and Peppas models to investigate the release mechanism. It was found that by varying the composition of PVA/Ge hydrogel and GA concentration, a significant difference was observed in drug release kinetics. FTIR spectroscopy and X-ray diffraction were used for the characterization of hydrogels. PVA/Ge hydrogel showed sustained release of the model drug at various pH values suggesting its potential use as a sustained drug delivery system.

A synthesized Schiff base ligand 4-{(Z)-[(2-hydroxy-1-naphthyl)methylene]amino}-4-antipyrene (H-NAPP) was confirmed by single crystal diffraction analysis. The H-NAPP was crystalized in the P 21 21 21 space group and orthorhombic crystal system. The Schiff base ligand H-NAPP bears potential donor sites and therefore it was reacted with transition metal ions Co2+, Ni2+, Cu2+, and Zn2+ to yield respective metal complexes. All reaction products were investigated by elemental analyses and IR spectroscopic techniques. The combined spectroscopic characterizations revealed the distorted square planar geometries for all the synthesized metal complexes. The metal complexes were further studied for their thermal stabilities using TG techniques and proved to be thermally cleaved in the temperature range of 30–1,000°C in air. Pseudo-mirrored 2D fingerprint plots were used for the short interatomic interactions in the crystal structure. The major short interatomic interactions involve the hydrogen bonding which covers the Hirshfeld surfaces {H···H, O···H and C···H}. The ligand and complexes were investigated for a potential α-glucosidase inhibitory activity. While relatively inactive throughout, some notable differences were observed and, surprisingly, the ligand was found to be more active than its complexes.