Inhibitory Potential Research Articles

High-Throughput Insilico Drug Screen against Mpox Targeted Proteins in Comparison with Repurposed Antiviral Drugs against Natural Compounds

The recent resurgence of the Monkeypox Virus (MPXV) has prompted increased efforts to discover effective antiviral treatments. This study utilized an in silico docking approach with CB Dock2 to assess both natural compounds and repurposed antiviral medications. We concentrated on several critical viral targets for inhibition, specifically VP39 2'-O Methyltransferase, viral topoisomerase-DNA complexes, and poxin. Our results identified a number of natural substances, including Physalin A, Sitoindoside IX, Withanolide, Shatavarin 1, Kutkoside, and Berberine HCl, as promising inhibitors. Tecovirimat was found to be the most effective among the repurposed antivirals. Notably, natural products like Withanolide, Sitoindoside IX, and Physalin A showed significant inhibitory potential based on their Vina scores and binding affinities, suggesting they may serve as alternative therapeutic options. Tecovirimat consistently proved to be the most powerful inhibitor among repurposed antivirals across all examined targets, reinforcing its importance in combating MPXV.

Targeted nanoliposomes of oncogenic protein degraders: Significant inhibition of tumor in lung-cancer bearing mice

With 60 % of non-small cell lung cancer (NSCLC) expressing epidermal growth factor receptor (EGFR), it has been explored as an important therapeutic target for lung tumors. However, even the well-established EGFR inhibitors tend to promptly develop resistance over time. Moreover, strategies that could impede resistance development and be advantageous for both EGFR-Tyrosine kinase inhibitor (TKI)-sensitive and mutant NSCLC patients are constrained. Based on the critical relationship between EGFR, c-MYC, and Kirsten rat sarcoma virus (K-Ras), simultaneous degradation of EGFR and Bromodomain-containing protein 4 (BRD4) using “Proteolysis Targeting Chimeras (PROTACs)” could be a promising approach. PROTACs are emerging class of oncoprotein degraders but very challanging to deliver in vivo. Compared to individual IC50s, strong synergism was observed at 1:1 ratio of BPRO and EPRO in NSCLC cell lines with diverse mutation. Significant inhibition of cell growth with higher cellular apoptosis was observed in 2D and 3D-based cell assays in nanomolar concentrations. EGFR activation assay revealed 47.60 % EGFR non-expressing cells confirming EGFR-degrading potential of EPRO. A lung cancer specific nanoliposomal formulation of EGFR and BRD4-degrading PROTACs (EPRO and BPRO) was prepared and characetrized. Successful encapsulation of the two highly lipophilic molecules was achieved in EGFR-targeting nanoliposomal carriers (T-BEPRO) using a modified hydration technique. T-BEPRO revealed a particle size of 109.22 ± 0.266 nm with enhanced cellular uptake and activity. Remarkably, parenterally delivered T-BEPRO in tumor-bearing mice showed a substantially higher % tumor growth inhibition (TGI) of 77.6 % with long-lasting tumor inhibitory potential as opposed to individual drugs.

Polypurine reverse hoogsteen hairpins as a therapeutic tool for SARS-CoV-2 infection

Although COVID-19 pandemic was declared no longer a global emergency by the World Health Organization in May 2023, SARS-CoV-2 is still infecting people across the world. Many therapeutic oligonucleotides such as ASOs, siRNAs or CRISPR-based systems emerged as promising antiviral strategies for the treatment of SARS-CoV-2. In this work we explored the inhibitory potential on SARS-CoV-2 replication of Polypurine Reverse Hoogsteen Hairpins (PPRHs), CC1-PPRH and CC3-PPRH, targeting specific polypyrimidine sequences within the replicase and Spike regions, respectively, and previously validated for COVID-19 diagnosis. Both PPRHs bound to their target sequences in the viral genome with high affinity in the order of nM. In vitro, both PPRHs reduced viral replication by more than 92% when transfected into VERO-E6 cells 24 hours prior infection with SARS-CoV-2. In vivo intranasal administration of CC1-PPRH in K18-hACE2 mice expressing the human ACE receptor protected all the animals from SARS-CoV-2 infection. The properties of PPRHs position them as promising candidates for the development of novel therapeutics against SARS-CoV-2 and other viral infections.

Potent α-glucosidase inhibitors with benzimidazole-propionitrile hybridization; synthesis, bioassay and docking study.

Background: Diabetes is characterized by a lack of insulin and insensitivity to insulin. In 2013, the global diabetes population was 382million, with 90% of them having type 2 diabetes (non-insulin-dependent). It is predicted that this number will increase to 592million by 2035.Aim: Here, we aimed to synthesize a series of benzimidazole-based derivatives B1-B32 with α-glucosidase inhibition potential as antidiabetic agents.Methods: Compounds B1-B32 were prepared in three three-step reactions, and the structures were elucidated using spectroscopic methods, namely 1H NMR, 13C NMR, MS and IR. Enzyme inhibition and kinetic study were done using commercial assay kits, and molecular docking study using autodock4.Results: Bioassay data showed that twenty-four out of the thirty-two tested compounds exhibited IC50 values ranging from 44 to 745μM, surpassing the standard molecule, acarbose (IC50: 750μM). it was determined that the best compound, B10, functions as a competitive inhibitor. Additionally, a molecular docking study provided insights into the interactions between the four most promising compounds (B5, B6, B10 and B28) and the active site residues within the enzyme.Conclusion: The tested compounds are interesting α-glucosidase inhibitors, which indicates the benefit of more bioassay studies, especially in vivo studies.

Mechanistic insights into β-glucuronidase inhibition by isoprenylated flavonoids from Centaurea scoparia: Bridging experimental and computational approaches

Exploring the intricate mechanisms underlying the inhibition of β-glucuronidase, particularly the enzyme produced by gastrointestinal bacteria, is essential for the development of novel therapeutic interventions and pharmaceutical advancements. Inhibiting bacterial β-glucuronidase can prevent the reactivation of harmful drug metabolites in the gut, thereby reducing associated toxicities. The inhibitory potential of four isoprenylated flavonoids from Centaurea scoparia against β-glucuronidase was intensively investigated by combined in vitro and in silico tools. The results of in vitro inhibitory activity showed that Compounds 1 and 3 exhibited the highest inhibitory activity, as evidenced by their low IC50 values of 3.65 ± 0.28 and 3.97 ± 0.11 μM, respectively. The enzyme kinetics analysis revealed that Compound 1 and the positive control drug (EGCG) follow a mixed inhibition mechanism. In contrast, compounds 3 and 4 exhibited a noncompetitive inhibition mode, as suggested by the intersection patterns observed in the Lineweaver-Burk plots. The docking studies corroborated the in vitro inhibitory assay results, with Compounds 1 and 3 demonstrating the lowest binding affinities and the highest extent of polar and hydrophobic interactions with residues in the enzyme's binding site. Utilizing a 200 ns molecular dynamics (MD) simulation, we examined the interaction dynamics between isolated flavonoids and β-glucuronidase. The analysis of multiple MD parameters revealed that compounds 1 and 3 maintained consistent trajectories and demonstrated significant energy stabilization when interacting with β-glucuronidase. These computational findings align with experimental results, highlighting the potential of compounds 1 and 3 as potent inhibitors for β-glucuronidase.

Engineering inhibitory repeat domains of Pin-II type proteinase inhibitors indicate their high structural-functional tolerance to mutagenesis

Plant proteinase inhibitors (PIs) are critical in defending against biotic stress. Most PIs contain an inhibitory repeat domain (IRD), which serves as the functional component, displaying a high degree of sequence and structural conservation. In this study, we examined the structural and functional resilience of IRDs using a combination of computational modeling and experimental validation. We have taken an evolution-based approach to enhance the PIs effectiveness of two previously identified Capsicum annuum IRDs, IRD4 and IRD10. Through in silico site-saturation mutagenesis of IRD4 and IRD10, we identified key sites associated with enhanced PI activity for targeted mutagenesis. Binding energy predictions for a mutant IRD library, tested against target proteases, suggested that positions R11 and N32 in IRD4 and N32 and H33 in IRD10 were promising candidates for further modification to improve inhibitory potential. Subsequent experimental validation revealed that the mutant proteins IRD4_R11K and IRD4_N32S exhibited stronger chymotrypsin inhibition than the wild-type (WT) IRD4. Similarly, the mutants IRD10_N32S and IRD10_H33 N demonstrated improved trypsin inhibition relative to the WT IRD10. These findings indicate that engineered IRD variants can tolerate structural changes while maintaining or enhancing their inhibitory activity against target proteases. Overall, this study demonstrates the potential of engineering PIs to increase their structural and functional resilience, offering new opportunities for biotechnological applications.

Enrichment of shortcrust pastry cookies with bee products: polyphenol profile, in vitro bioactive potential, heat-induced compounds content, colour parameters and sensory changes

Bee products, including bee pollen (BP) and bee bread (BB) are natural sources that contain a diverse range of bioactive compounds. The objective of this study was to investigate the potential of BP and BB to enhance the functional properties of shortcrust pastry cookies. The impact on BP and BB on the colour parameters, polyphenolic compounds content, heat-induced compounds content (acrylamide, furfural, 5-hydroxymethylfurfural (HMF)), antioxidant properties, and inhibitory effects against advanced glycation end products (AGEs) formation and acetylcholinesterase (AChE) activity was examine by enriching cookies with 3 and 10% of BP or BB. The incorporation of BP or BB resulted in a notable darkening of the cookies. The spectroscopic and chromatographic analyses revealed that the cookies enriched with bee products exhibited an elevated content of phenolic compounds. The antioxidant activity (AA) of the enriched cookies exhibited an average increase of 2- to 3-fold in the ABTS test and 2-fold in the DPPH test. All cookies exhibited inhibitory potential against AGEs formation, witch inhibitory rates ranging from 10.64 to 46.22% in the BSA-GLU model and 1.75–19.33% in BSA-MGO model. The cookies enriched with 10% BP were characterised by to the highest level of AChE activity inhibition (13.72%). The incorporation of BB and BP resulted in elevated concentration of acrylamide, furfural, and HMF. Our findings suggest that bee products may serve as a valuable addition to food ingredients, significantly enhancing the functional properties of shortcrust pastry cookies. However, further investigation is necessary to address the increased level of heat-induced compounds.

Quercetin: Potential antidiabetic effects through enzyme inhibition and starch digestibility

AbstractDiabetes mellitus involves high blood sugar levels due to insufficient insulin action. Furthermore, enzymes such as α‐amylase and α‐glucosidase break down carbohydrates into glucose, leading to postprandial hyperglycemia. Flavonoids, particularly quercetin, inhibit these enzymes, slowing carbohydrate digestion and reducing glucose absorption. Quercetin has significant hypoglycemic effects with inhibitory concentration (IC50) values comparable to acarbose, a standard inhibitor, suggesting its potential as a natural alternative for diabetes management. In silico models, including molecular docking, molecular dynamics (MD) simulations, and quantitative structure‐activity relationship (QSAR) approaches, help researchers understand the molecular interactions of therapeutic agents. These techniques identify potential inhibitors, determine enzyme‐inhibitor structures, and calculate binding energies, correlating findings with in vitro or in vivo data. Molecular docking predicts molecular orientations, MD simulations offer insights into enzyme–inhibitor dynamics, and QSAR models predict inhibitory potential based on structural properties. Studies have shown that quercetin effectively inhibits α‐glucosidase and α‐amylase by forming hydrogen bonds with specific amino acid residues. Quercetin interacts with starches and reduces their digestibility, increases the formation of resistant starch, lowers the glycemic index, and inhibits digestive enzymes. Studies show that the effects of quercetin on starch digestion vary with concentration and type of starch, and its incorporation into foods such as bakery products, pasta, etc. can significantly decrease starch hydrolysis. The incorporation of quercetin into starch matrices may aid in the development of functional foods aimed at improving glycemic control.

Diversely functionalized benzopyran scaffolds as potential lead candidates for treating Alzheimer's disease and diabetes

The current study deals with the preparation of polyfunctional benzopyran derivatives 1–25, synthesized by the condensation of 2,4-dihydroxy benzophenone, substituted aldehydes, and malononitrile. These compounds were evaluated for their inhibitory potential against AChE, BChE, α-amylase, and α-glucosidase enzymes, as well as for DPPH radical scavenging activity. Among 25 compounds, 1, 4–6, 14, 15, and 25 showed excellent inhibition against AChE (IC50 = 5.30 - 37.14 µM) and BChE (IC50 = 8.20 - 43.13 µM), compared to standard donepezil (IC50 = 40.05 for AChE; 45.00 µM for BChE), respectively. Moreover, compounds 2, 3, 11, and 12 inhibited α-amylase (IC50 = 1.88 - 11.42 µM) and α-glucosidase (IC50 = 2.54 - 8.36 µM) with greater potency than the standard acarbose (IC50 = 14.65 µM). Kinetic studies of the active compounds were also carried out to find the mode of inhibition. Furthermore, molecular docking was performed to determine the ligands' interaction with the enzyme's active site. In addition, compounds 9, 19, and 21 exhibited significant DPPH radical scavenging activity (SC50 = 44.88 - 64.61 µM) compared to BHT (SC50 = 66.34 µM). Thus, this study suggests that the reported compounds hold the potential to be further advanced as lead anti-Alzheimer and anti-diabetic agents.

Harnessing Phytochemicals to Regulate Catalytic Residues of Alpha-Amylase and Alpha-Glucosidase in Type 2 Diabetes.

Type 2 diabetes (T2D), also known as non-insulin-dependent diabetes mellitus, represents the prevailing manifestation of diabetes, encompassing a substantial majority of cases, ~90-95%. Plant-derived antidiabetic leads are being intensively explored due to their safety and effectiveness. The main objective of the present study is to evaluate the anti-diabetic potential of the traditional formulation Karisalai Karpam through in-vitro and in-silico investigations. The in-vitro and in-silico investigation of traditional polyherbal preparation Karisalai Karpam (KK) chooranam were performed to ascertain its inhibitory potential against α-amylase and α-glucosidase enzymes along with antioxidant (DPPH and ABTS) and phytochemical analysis. The results of enzyme inhibitory activity of KK witnessed highest activity against α-glucosidase enzyme with a percentage inhibition of 84.66 ± 2.50% (IC50,187.9 ± 5.79 μg/ml) followed by moderate level of α-amylase inhibition exhibited with 72.94 ± 3.66% (IC50, 241.6 ± 9.76 μg/ml). Additionally, the strongest antioxidant activity was observed in quenching DPPH• (IC50,154.8 ± 14.53 μg/ml) and ABTS+• radicals (IC50,148.6 ± 29.74 μg/ml). The outcome of the molecular docking studies indicated that among the 17 compounds analysed, the lead such as acalyphin, apigenin, humulene, and indirubin exhibited a prominent binding affinity over the residual binding site of α-glucosidase. It's important to note that the catalytic site of the enzyme α-amylase is primarily occupied by amyrin, apigenin, arjunolic acid, β-sitosterol, geraniol, and tricetin. In conclusion, the formulation KK demonstrates robust alpha-glucosidase and alpha-amylase inhibitory activity. It's also worth noting that the formulation exhibits noteworthy antioxidant properties, which could provide additional health benefits. The binding mode and energies of the identified phytochemicals against the target enzymes further support the formulation's antidiabetic potential.

Screening of anti-diabetic potential of the siddha formulation sambirani poo kuligai by in-vitro alpha glucosidase enzyme inhibition assay

Background: Noninsulin-dependent diabetes mellitus (NIDDM) is a common disease of the endocrine system caused by the decreased secretion of insulin by the pancreatic Langerhans beta cell or by the lowering of insulin resistance due to excessive absorption of glucose. The Siddha system of medicine is a traditional medical system that uses a scientific and holistic approach to provide preventive, promotive, curative, rejuvenative and rehabilitative health care. According to Siddha literature, diabetes is known as Innippu Neer, Madhumegam and Neerizhivu. The various reasons for the cause of this disease are attributed to foodhabits and lifestyle changes and also due to hereditary causes. One of the therapeutic approaches is to decrease the postprandial hyperglycemia by retarding the absorption of glucose through the inhibition of carbohydrate-hydrolyzing enzymes, such as a-amylase and ?-glucosidase. ?-Glucosidase are enzyme that catalyze the absorption of digested glucose from dietary polysaccharides in the small intestine. Aim: The aim of the present study is to evaluate the anti-diabetic potential of the siddha formulation of Sambirani Poo Kuligai(SPK) by alpha glucosidase enzyme inhibition assay. Method: The spectrophotometric assay method was used to find alpha glucosidase inhibitory activity. Results: SPK showed presence of alpha glucosidase inhibitory potential with the maximum inhibition of about 41.74 ± 3.578 % and the corresponding IC50 is 606.5 ± 49.51?g/ml. Conclusion: This in-vitro study revealed the presence of the alpha glucosidase activity in the siddha formulation Sambirani Poo Kuligai possesses antidiabetic activity

Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Graft-versus-host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug-drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics. This study aimed to assess the impact of inflammation, as indicated by C-reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no-to-mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation. The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.

Protein hydrolysates with ACE-I inhibitory activity from amaranth seeds fermented with Enterococcus faecium-LR9: Identification of peptides and molecular docking

One of the causes of hypertension is the activity of angiotensin-I converting enzyme (ACEI), making its inhibition a crucial strategy for controlling the disease. Protein hydrolysates are a known source of bioactive peptides that contribute to ACE-I inhibition. This study aims to evaluate the ACE-I inhibitory activity of amaranth seed hydrolysates after fermentation with Enterococcus faecium-LR9 and to compare it with Leuconostoc mesenteroides-18C6 and enzymatic hydrolysis (Alcalase®). The fermentation strategy with LR9 proved to be more effective in inhibiting ACE-I (79.1 ± 2.6 %) in vitro compared to 18C6 (68.0 ± 9.8 %) and enzymatic hydrolysis (69.4 ± 1.2 %). Consequently, these protein hydrolysates were subjected to in silico analysis, identifying 125 novel peptides. Bioinformatics and molecular docking analyses revealed 10 peptides with high ACE-I inhibitory potential. Among them, the IFQFPKTY and VIKPPSRAW peptides stood out. Therefore, E. faecium-LR9 is a promising strain for the release of bioactive peptides from seed storage proteins.

Phytochemical Profiles and Biological Activities of Five Wild Camellia Species from Ta Dung, Vietnam.

The C. luuana Orel & Curry (TD3), C. furfuracea (Merr.) Cohen-Stuard (TD4), C. bidoupensis Truong, Luong & Tran (TD6), C. sinensis (L.) Kuntze (TD7), and C. kissii var. spp (TD8), have been traditionally used as a health-promoting beverage by local people in Ta Dung, Dak Nong. Despite their potential health benefits, further scientific data on biological and phytochemical properties of these plants is needed. To address this issue, this study was conducted to investigate phytochemical and biological properties of five Camellia species extracts, using DPPH, ABTS radical scavenging, copper chelating (Cu-chelator), and tyrosinase inhibition (TI), α-amylase (Al-AI), and α-glucosidase (Al-GI) analyses. As results, ten compounds were identified using UPLC method, in which catechins (mainly EGCG and catechin (Cat)), were the most prevalent, and followed by chlorogenic acid (ChlA), quercitrin (Querci), rutin, and quercetin (Querce). Additionally, multiple factor analysis (MFA) also revealed that TD7, TD3, and TD4 containing high TPC, TFC, high concentrations of EGCG, ChlA, and caffeine were responsible for their high DPPH, ABTS radical scavenging activities, as well asTI, Al-AI and Al-GI. Furthemore, TD6 and TD8, possessing elevated levels of Apig, Querci, Rutin, Querce, Cat, and EA, exhibited a high Cu-chelator property, but a weak enzyme inhibition. From all above-mentioned results, the antioxidative and enzyme inhibitory potentials of Camellia species extracts collected in Dak Nong province in Vietnam were scientifically demonstrated paving a pathway to develop health supplement in further studies.

Synthesis, spectral characterization and biological activities of o,o'-dihydroxyazo compounds containing gallic acid: Molecular docking and dynamics simulation and MM-PBSA studies

In the investigation, diazonium derivatives of 2-aminophenol, 2-amino-4-methylphenol, 2-amino-4-chlorophenol, and 2-amino-5-nitrophenol reacted with gallic acid to produce four distinct o,o'-dihydroxyazo compounds. Description of the o,o'-dihydroxyazo compounds that were produced identified the substituent spectrum data using UV–Vis, FT-IR, NMR spectroscopy and MS spectrometry methods. The UV–Vis behaviors of compounds in ethanol and DMSO were noted at various pH values. The antioxidant, antimicrobial, and urease inhibitory activities of the compounds were determined spectrophotometrically and compared to standard compounds. The DPPH˙ scavenging and metal chelating activities of compound 4b were 2.17 ± 0.04 and 11.62 ± 0.64 μg/mL, respectively. Compounds exhibited an effective antibacterial activity against B. cereus. The urease inhibition capacity of compound 4c (IC50: 4.79 ± 0.01 μg/mL) was more effective than thiourea (IC50: 20.04 ± 0.16 μg/mL). Moreover, molecular docking calculations were used to assess the urease inhibition potentials, inhibition kinetics, and interactions of the synthesized compounds with antimicrobial enzymes and urease. The compounds had substantial impacts on density functional theory (DFT), molecular electrostatic potential (MEP), inhibition kinetics, enzyme inhibition, and PASS prediction tests. For this reason, molecular dynamics simulation and MM-PBSA energy calculation were performed to assess the compounds' stability during urease binding.As a result, the effective pharmacological properties of the newly synthesized o,o'-dihydroxyazo compounds were revealed by different in vitro bioactivity tests and in silico calculations.

Allelopathic Potential of Volatile Oils from Mentha piperita and Chrysanthemum coronarium Growing in Western Algeria

Background: The allelopathic effects of the essential oils of M. piperita and C. coronarium on seed germination of two wheat species qualify them as bio-herbicides. Objective: In order to search for natural plant-based products that may have herbicidal action, we selected two plant species, M. piperita and C. coronarium, to evaluate the allelopathic potential of their essential oils on wheat seed germination of two wheat species. Methods: Aerials parts of M. piperita and C. Coronarium were subjected to hydrodistillation using a Clevenger-type apparatus to extract essential oils, followed by characterization using gas chromatography coupled with mass spectrometry. Bioassays were conducted with ethanol as the organic solvent, employing three concentrations (0.25, 0.5, and 0.75 μl/ml of oil/ethanol) to assess their effects on the seed and seedling growth of two wheat species. Results: Under laboratory conditions, extracts of Mentha piperita and Chrysanthemum coronarium oils at varying concentrations (0.25 μl, 0.5 μl, and 0.75 μl) were examined for their effects on two wheat species (Triticum durum L. and Triticum aestivum L.). The yields of the obtained oils were 1.19% and 0.25%, respectively. The chemical composition of the essential oils extracted from M. piperita and C. coronarium was dominated by oxygenated monoterpenes, representing 97.5% and 94.9%, respectively. The tested essential oils strongly inhibit seed germination and seedling growth (root length LR and shoot length LPA) of both wheat species studied. The inhibition increased as the oil concentration increased, although this increase differed between the two species. This study has shown that the tested essential oils possess an interesting inhibitory allelopathic potential. result: The oils extracts of M. piperita and C. coronarium at different concentrations (0.25 μl, 0.5 μl, and 0.75 μl) were tested on two varieties of wheat (Triticum durum L. and Triticum aestivum L.) under laboratory conditions. The yields of the obtained oils are 1.19% and 0.25%, respectively. The chemical composition of the essential oils (EOs) of M. piperita and C. coronarium is dominated by oxygenated monoterpenes, representing 97.5.% and 94.9%, respectively. The tested EOs strongly inhibit seed germination and seedling growth (LR and LPA) of both wheat varieties studied. The inhibition increases as the oil concentration increases, although this increase is not comparatively similar for the two species. This study has shown that the tested EOs possess an interesting inhibitory allelopathic potential. Conclusion: The findings of this study indicate that the tested essential oils possess promising allelopathic properties, suggesting them as natural bio-herbicides.

One-Step Soft Agar Enrichment and Isolation of Human Lung Bacteria Inhibiting the Germination of Aspergillus fumigatus Conidia

Fungi of the genus Aspergillus are widespread in the environment, where they produce large quantities of airborne conidia. Inhalation of Aspergillus spp. conidia in immunocompromised individuals can cause a wide spectrum of diseases, ranging from hypersensitivity responses to lethal invasive infections. Upon deposition in the lung epithelial surface, conidia encounter and interact with complex microbial communities that constitute the lung microbiota. The lung microbiota has been suggested to influence the establishment and growth of Aspergillus spp. in the human airways. However, the mechanisms underlying this interaction have not yet been sufficiently investigated. In this study, we aimed to enrich and isolate bacterial strains capable of inhibiting the germination and growth of A. fumigatus conidia from bronchoalveolar lavage fluid (BALF) samples of lung transplant recipients using a novel enrichment method. This method is based on a soft agar overlay plate assay in which bacteria are directly in contact with conidia, allowing inhibition to be readily observed during enrichment. We isolated a total of five clonal bacterial strains with identical genotypic fingerprints, as shown by random amplified polymorphic DNA PCR (RAPD–PCR). All strains were identified as Pseudomonas aeruginosa (strains b1–b5). The strains were able to inhibit the germination and growth of Aspergillus fumigatus in a soft agar confrontation assay, as well as in a germination multiplate assay. Moreover, when compared with ten P. aeruginosa strains isolated from expectoration through standard methods, no significant differences in inhibitory potential were observed. Additionally, we showed inhibition of A. fumigatus growth on Calu-3 cell culture monolayers. However, the isolated P. aeruginosa strains were shown to cause significant damage to the cell monolayers. Overall, although P. aeruginosa is a known opportunistic lung pathogen and antagonist of A. fumigatus, we validated this novel one-step enrichment approach for the isolation of bacterial strains antagonistic to A. fumigatus from BALF samples as a proof-of-concept. This opens up a new venue for the targeted enrichment of antagonistic bacterial strains against specific fungal pathogens.

In vitro Anti-Diabetic and Antioxidant Potential of the Siddha formulation Mega Sanjeevi Chooranam

Background: The increasing prevalence of type 2 diabetes mellitus (T2DM) presents a significant public health challenge due to its long-term complications and its role as a primary risk factor for cardiovascular diseases, which have both economic and social implications. Plant-derived antidiabetic drugs are being extensively studied due to their safety and efficacy. The main objective of the present study is to evaluate the anti-diabetic and anti-oxidant potential of the formulation Mega Sanjeevi Chooranam (MSC) through in-vitro investigation. Materials and Methods: The in vitro investigation of traditional siddha formulation MSC were performed to ascertain its inhibitory potential against α-amylase and α-glucosidase enzymes along with antioxidant analysis. Results: The MSC displayed the highest activity against α-amylase enzyme, with a percentage inhibition of 73.44 ± 6.87% (IC50, 299.4 ± 27.27 μg/ml), followed by a moderate level of α-glucosidase inhibition at 48.89 ± 13.38% (IC50, 402.2 ± 86 μg/ml). Furthermore, the MSC exhibited the strongest antioxidant activity in quenching ABTS● radicals (IC50, 110.1 ± 18.6 μg/ml), followed by DPPH● (IC50, 144.4 ± 36.8 μg/ml), H2O2● (IC50, 172.7 ± 39.3 μg/ml), and NO● radicals (IC50, 238.4 ± 58.56 μg/ml). Conclusion: In conclusion the formulation MSC demonstrated the significant antioxidant activity and effectively inhibited α-amylase and α-glucosidase enzyme activities. Further study is needed to isolate bioactive phytoconstituents and determine the molecular mechanism behind their antidiabetic effect.

Investigating the efficacy of naphthalene-thiazole hybrid hydrazones as α-glucosidase inhibitors

In this study, a series of hydrazone derivatives containing naphthalene and thiazole hybrids were synthesized through the condensation of (E)-4-methyl-2-(2-(naphthalen-1-ylmethylene)hydrazineyl) thiazole-5-carbohydrazide with various carbonyl compounds, including aldehydes and ketones, whether carbocyclic aromatic or heterocyclic, using a grinding method with drops of acetic acid. The elucidation of the structures of the synthesized hydrazone derivatives was achieved through the analysis of NMR, IR, and mass spectrometry data. All the newly prepared compounds were assessed for their in vitro α-glucosidase inhibition profiles and the results revealed a diverse range of inhibitory potentials, ranging from 9.3 ± 1.0 to 70.5 ± 1.8 μM, in contrast to the reference acarbose (with an IC50 value of 45.2 ± 1.3 μM). In an attempt to explain the observed inhibitions of synthesized naphthalene containing thiazole compounds, molecular docking was performed to determine the binding modes between the synthesized compounds from one side and the active residues of α-glucosidase from the other side. Compounds 4d, 4e, 4c, and 8 demonstrated the strongest binding affinities, with binding energies of -10.5, -9.8, -9.6, and -9.5 kcal/mol, respectively.

UPLC-HRMS/MS Guided Isolation and NMR Investigation of Major Flavonoids from Enarthrocarpus strangulatus Boissier (Brassicaceae) with In Vitro Enzymes Inhibitory Potential.

Various members of the family Brassicaceae are economically importantand traditionally used to treat many disorders. Among the family members, Enarthrocarpus strangulatusBoissier is a common Egyptian species that was rarely studied. Consequently, the current study aims to characterize its phytochemical composition and assess its potential bioactivity comprehensively. A metabolomics approach integrating UPLC-HRMS/MS-based molecular networking enabled the dereplication of 91 metabolites, including primary (i.e. organic acid, amino acids, fatty acids, and phospholipids) and secondary metabolites (i.e. glucosinolates, phenolic acids, and flavonoids). Among the 91 annotated features, 13 major metabolites were fully characterized following their isolation and purification. Exclusive of only three flavonoids, all the detected metabolites are described for the first time within this species. Furthermore, the crude extract and four major isolated flavonoids were subjected to in vitro biological screening, including antioxidant, radical scavenging, anti-diabetic, anti-Alzheimer's, and anti-inflammatory activities. It was noticed that nobiletin (61) exhibited the highest antioxidant and anti-Alzheimer's activities. At the same time, isorhamnetin 3-O-glucose (51) showed the highest anti-diabetic activity compared to the other isolated flavonoids and the total extract itself. Regarding the anti-inflammatory activity, no obvious differences were detected numerically among all studied flavonoids.