A phytochemical investigation of Euphorbia tirucalli Linn. (F. Euphorbiaceae) latex resulted in the isolation of five known compounds, namely euphol (1), euph-8-enol (2), gallic acid (3), methyl gallate (4), and rutin (5). The chemical structures of the isolated compounds were unambiguously established by extensive nuclear magnetic resonance (NMR) spectroscopic analysis. The antimicrobial activities of these compounds were evaluated against Klebsiella pneumoniae (ATCC 13883), extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, and carbapenem-resistant K. pneumoniae using the microbroth dilution method. Among the tested compounds, methyl gallate (4) exhibited the strongest activity against K. pneumoniae (ATCC 13883) with a minimum inhibitory concentration (MIC) of 0.01 mM, while euphol (1) showed the highest activity against ESBL K. pneumoniae (MIC = 13.12 mM). Notably, euph-8-enol (2) demonstrated the most potent inhibitory effect against carbapenem-resistant K. pneumoniae, with an MIC of 0.69 mM. Network analysis identified 33 host-response targets relevant to Klebsiella infection, enriched in pattern-recognition receptor signaling and inflammatory defense programs, particularly the Toll-like receptor and NOD-like pathways, alongside cytokine/chemokine-mediated recruitment and inflammasome-associated signaling. Molecular docking against Klebsiella pneumoniae LpxH (PDB: 8QK2) showed the strongest predicted affinity for euphol (1) (-8.13 kcal mol-1). MD simulation of the euphol (1)-LpxH complex over 100 ns supported overall system stability, evidenced by a stable protein backbone RMSD, maintained compactness (R g), equilibrated potential energy, and intermittent hydrogen bonding consistent with predominantly hydrophobic binding. Collectively, these findings suggested that E. tirucalli, with euphol as the top-ranked binder, could provide structural starting points for further investigation for anti-Klebsiella development, warranting further in vitro validation of LpxH inhibition and antibacterial efficacy against resistant Klebsiella strains.

Parkinson's disease (PD) presents as a progressive deterioration of dopaminergic neurons, a process closely associated with increased oxidative damage due to accumulated reactive oxygen species, leading to weakened antioxidant defenses and ultimately neuronal dysfunction. Currently, no definitive approach exists to counteract the degeneration of dopaminergic neurons in PD. The use of Tamarix aphylla as a protective agent against Parkinson's disease is not well studied yet. In this study, a rotenone-induced rodent model was utilized to examine the neuroprotective potential of T. aphylla extract. The chemical composition of T. aphylla leaves was analyzed through LC-HR-ESI-MS profiling, identifying 13 metabolites from various chemical categories. Furthermore, the research incorporated the STRING database and Cytoscape software to perform a protein-protein interaction (PPI) analysis, pinpointing essential hub proteins involved in neuroprotection and inflammation in PD. Molecular docking and a 150 ns molecular dynamics simulation were performed to assess the interaction of plant-derived compounds with the Sirt-1 catalytic domain. Compound 12, one of the bioactive compounds found in T. aphylla, exhibited strong binding affinity and stability throughout the 150 ns simulation, highlighting its role as a neuroprotective agent. This study underscores the fusion of computational and experimental techniques to investigate natural neuroprotective compounds, providing potential therapeutic strategies for PD treatment by influencing key pathways linked to oxidative damage and neuroinflammation.

This study has investigated the phytochemical composition and therapeutic potential of the Red Sea soft coral Sinularia levi. Five compounds (1-5) comprising three glyceryl derivatives, a ceramide, and a diterpene were isolated and characterized. To elucidate their role in metabolic syndrome, an integrated network pharmacology and structure-based modeling workflow was employed. This approach identified 45 shared targets between S. levi metabolites and disease proteins, clustered into inflammatory and metabolic nodes, with α-glucosidase (GAA) emerging as a primary target. Molecular docking against GAA (PDB: 5NN8) identified 1-O-nonacosylglycerol (2) as the most potent ligand (-8.5 kcal mol-1), stabilized by a unique glycerol-head polar clamp involving Glu139 and Lys137. The stability of this complex was confirmed through a 100 ns MD simulation, which demonstrated sustained equilibrium and persistent hydrogen bonding. In vitro assays revealed that the total extract possesses significant antioxidant activity (DPPH IC50 = 18.66 µg mL-1), and the isolated compounds exhibited selective enzyme inhibition. In which, 1-O-nonacosylglycerol (2) proved to be the most effective α-glucosidase inhibitor (IC50 = 326.77 µg mL-1), whereas glyceryl pentacosanoate (5) showed the highest activity against pancreatic lipase (IC50 = 170.75 µg mL-1). These findings suggest that S. levi metabolites, particularly 1-O-nonacosylglycerol, represent preliminary screening for managing postprandial glucose levels.

Majorana hortensis Moench, a member of the family Lamiaceae, is a medicinal and aromatic plant, cultivated in several parts of the world; it contains several classes of secondary metabolites with valuable biological activities. The study investigates its metabolomic profiling and anti-biofilm activity, focusing on its tissue culture-derived secondary metabolites and molecular docking potential. Callus cultures were initiated using auxins (2,4-dichlorophenoxy acetic acid 2,4-D, naphthalene acetic acid NAA, indole-3-acetic acid IAA) and cytokinins (kinetin KIN), then elicitation by chemical (proline, salicylic acid, phenylalanine, NaCl) and physical (UV-C) agents to enhance phenolic and flavonoid production. LC-QTOF-MS/MS analysis identified 70 metabolites, including terpenes, flavonoids, hydroxycinnamic acids, and lipids, with extract of 5 mg phenylalanine + 1000 mg NaCl-treated sample (extract 4) exhibiting the highest total phenolics and flavonoids, doubling the content of the mother root plant. The extract demonstrated potent anti-biofilm activity, significantly inhibiting biofilm formation in MRSA USA300 (89.2% +/- 1.1%) and A. baumannii (82.7% +/- 7.6%), while also facilitating substantial biofilm detachment (88.6% +/- 4.8% and 73.2% +/- 9.1%, respectively,(Two Way ANOVA, Tukey's post-test P < 0.05). Molecular docking revealed that rosmarinic acid dihexoside has the highest binding activity to S. aureus SarA and A. baumannii CsuE targets, suggesting its role in disrupting biofilm formation. Overall, this research suggests the utility of tissue culture and elicitation strategies to enhance the production of valuable secondary metabolites in Majorana hortensis, therebyoffering promising avenues for developing natural anti-biofilm agents. Further studies are warranted to explore the broader applications of these compounds against other resistant pathogens.

This study aims to evaluate the in vitro anti-acetylcholinesterase, antioxidant, and antibacterial activities of the essential oil (EOPC) extracted from Tunisian Phalaris canariensis seeds and to determine the potential interactions of its major compounds. The EOPC underwent GC-MS analysis and a total of 56 compounds were identified, accounting for over 89.3% of the total oil. The main components identified were octadecane, carvacrol, delta-decalactone, 2-ethenylfuran, tricosane, thymoquinone, nonadecene, camphor, E-damascenone, and beta-eudesmol. This EOPC showed substantial antioxidant properties, as demonstrated by reducing power, DPPH, and total antioxidant capacity assays. It also displayed significant anti-acetylcholinesterase activity (PI=67.5%) and strong bactericidal efficacy, with inhibitory zone diameters ranging from 14.0 +/- 0.8 to 21.0 +/- 1.1 mm. A molecular docking study was conducted to better understand the mechanisms of bioactive substances, specifically thymoquinone and carvacrol, in terms of their inhibitory action on the acetylcholinesterase enzyme. The results suggest that the EOPC has the potential to be a valuable source of biomolecules for food and pharmaceutical applications.

In our search for new antimicrobial agents from nature, the initial antimicrobial effect of the marine-derived fungus Aspergillus terreus strain 15F6 against Staphylococcus aureus and MRSA demonstrated promising effect. Large scale fermentation and bio-guided isolation led to the isolation of two natural butyrolactones (1 and 2). To study the structure activity relationship, we have prepared a few semisynthetic butyrolactone analogues with different substituents. Surprisingly, the semisynthetic analogue 1a demonstrated promising antimicrobial effect against MRSA but not S. aureus with MIC below 3 mu M. Using in silico studies to unlock the potential mechanisms behind these observations, we have found that the new semisynthetic butyrolactone analogues successfully bind to the Mur-B binding site.

Objectives Bacterial resistance to current antibiotics is mounting at an alarming rate, making many conventional antibiotics ineffective and posing a serious worldwide health threat; thus, there is a crucial need for exploration of novel antimicrobial leads from unusual sources, particularly the marine environment, which produces unique chemical compounds with promising therapeutic potential. This study aims to purify antimicrobial compounds from the ethyl extract of the fungus Alternaria rosae DY-79, characterize their chemical structures, and evaluate their antimicrobial effects against pathogenic microbes. Methods The antimicrobial fraction of the fungal culture extract was partitioned, and purified, yielding two unreported compounds, alternoic acids A ( 1 ) and B ( 2 ). Their structural determination was conducted using NMR and (+)-HRESIMS spectral analyses. Antimicrobial activities were measured against Escherichia coli , Staphylococcus aureus , methicillin-resistant S. aureus (MRSA), and Candida albicans . Results Alternoic acids A ( 1 ) and B ( 2 ) were identified as (4 E ,6 E )-6-(methoxycarbonyl)-2,4-dimethylocta-4,6-dienoic acid and (3 E ,6 E )-6-(methoxycarbonyl)-2,4-dimethylocta-3,6-dienoic acid, respectively. Compound 1 showed no MRSA activity, with inhibition zones of 14.2–17.2 mm against S. aureus , E. coli , and C. albicans (MICs: 21.3, 21.3, and 10.7 µg/mL, respectively). Compound 2 exhibited anti-MRSA activity (17.2 mm; MIC = 8.3 µg/mL), weaker zones against bacteria (12–12.2 mm; MICs = 21.3 µg/mL), and antifungal effects (17.3 mm; MIC = 10.7 µg/mL). Compared to imipenem (MRSA MIC = 0.75 µg/mL; S. aureus zone = 29.3 mm), compound 2 was less potent bacterially but showed antifungal activity comparable to clotrimazole (17.8 mm; MIC = 0.17 µg/mL). Significant differences ( P < 0.001) were observed versus imipenem. Conclusion Compound 2 demonstrates notable anti-MRSA activity (weaker than imipenem), while both compounds show antifungal effects against C. albicans with inhibition zones like clotrimazole but weaker MICs. Alternoic acids A and B may serve as lead scaffolds for antimicrobial optimization, particularly for antifungal applications, warranting further mechanistic studies.

Marine-derived species of the genus Alternaria are widely distributed across diverse aquatic habitats, functioning as pathogens, endophytes, and saprophytes. These fungi are notable for their ability to produce structurally diverse secondary metabolites with potent bioactivities. Between 2003 and 2023, a total of 67 marine-derived Alternaria species were reported and investigated, collectively yielding 319 compounds. Most of these fungal isolates were from Chinese marine territories (53 species; ~79%), followed by isolates from Korea, Japan, India, Egypt, Saudi Arabia, and oceanic regions such as the Atlantic and Pacific. The fungal isolates were mainly obtained from marine plants (26 isolates) and marine animals (23 isolates), with additional sources including sediments (13) and seawater (3). Among the metabolites investigated in different screens, approximately 56% demonstrated measurable bioactivities, with anti-inflammatory (51 active compounds), antimicrobial (41 compounds), cytotoxic (39 compounds), and phytotoxic (52 compounds) activities being the most frequently reported. Additionally, compounds with antiparasitic, antidiabetic and antioxidant effects are reported. The chemical diversity of Alernaria-derived compounds spans multiple structural groups, including nitrogenous compounds, steroids, terpenoids, pyranones, quinones, and phenolics. Notably, compounds such as alternariol, alternariol monomethyl ether, and alternariol-9-methyl ether exhibit broad pharmacological potential, including antibacterial, antifungal, antiviral, immunomodulatory, and anticancer effects. Several metabolites also modulate cytokine production (e.g., IL-10, TNF-α), underscoring their relevance as immunomodulatory agents. Taken together, marine-derived Alternaria compounds represent a prolific and underexplored source of structurally and biologically diverse secondary metabolites with potential applications in drug discovery, agriculture, and biotechnology. This review provides an updated and comprehensive overview of the chemical and biological diversity of Alternaria metabolites reported over the past two decades, emphasizing their biomedical relevance and potential to inspire further research into their ecological functions, biosynthetic mechanisms, and industrial applications.

Phytochemical investigation of the total ethanolic extract and various derived fractions of Arctotis aurantiaca roots resulted in the isolation of eight chemically diverse metabolites, including two fatty alcohols [n-octacosanol (1) and n-pentacosanol (2)], three sesquiterpene lactones [9,8-hydroxy-11 ,8,13-dihydrozaluzanin C (3), 11a, 13-dihydroglucozaluzanin C (5), and ixerin F (6)], one coumarin [6-Methoxy-7-hydroxycoumarin (scopoletin) (4)], one lignan [4,8-dimethoxyeudesmin (7)] and one phenolic acid derivative [3,5-dicaffeoylquinic acid methyl ester (8)] using different chromatographic techniques. The antibacterial activity of these isolated compounds was investigated against Escherichia coli ATCC 25,922 using well-diffusion assay technique. Among the tested compounds, compound (6) exhibited the strongest antibacterial activity with a MIC of 1.7 mu g/mL, whereas compound (1) was the least potent with a MIC of 218.2 mu g/mL compared to gentamicin (MIC= 2 mu g/mL) as a positive control. Additionally, molecular docking and 140 ns molecular dynamics (MD) simulations were performed to evaluate the binding interactions of the isolated compounds with E. coli DNA gyrase A. The results indicated that ixerin F (6) showed strong binding affinity and stability over 140-nanosecond simulation, highlighting its potential as an antibacterial agent. This study underscores the integration of computational and experimental methods to develop novel antibacterial strategies against E. coli, presenting A. aurantiaca as a candidate antibacterial plant by targeting bacterial DNA gyrase, a key enzyme involved in regulating DNA topology and supercoiling, which indirectly impacts essential cellular processes such as replication and transcription. (c) 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

A plethora of studies have been explored to identify effective, safe, and economical alternatives to potentially hazardous antibiotics. Natural extracts of marine organisms and their secondary metabolites are among the intriguing study topics to address this growing concern. This study aimed to investigate the effects of ten purified metabolites isolated from the isolated marine-derived bacterial strain, Enterobacter cloacae GH1 on various resistant pathogens. E. cloacae GH1 was isolated from Red Sea alga, Cystoseira myrica, together with other strains and has been chosen as a promising isolate based on its high microbial inhibition zones towards tested Gram-positive and-negative bacteria. Moreover, metabolomic analysis using (LC-HRESIMS) was conducted for different fractions of ethyl-acetate extract of E. cloacae GH1 for de-replication of biosynthesized and/or produced metabolites. Most de-replicated metabolites were isolated and purified using advanced preparative techniques followed by subsequent antimicrobial and docking studies. Results indicated that ethyl-acetate extract of E. cloacae GH1 significantly increased microbial growth inhibition, especially Staphylococcus aureus and Sarcina maxima. Moreover, metabolomic profiling showed the presence of diverse phytochemicals, mostly diketopiprazines. In addition, purification of the extract afforded 8 diketopiperazine derivatives, namely cyclo(S-Pro-S-Tyr) (E1), cyclo(S-Pro-S-Val) (E2), Brevianamide F (E3), cyclo(S-hyp-S-Pro-S-Phe) (E4), cyclo(R-hy-S-Pro-R-Phe) (E5), cyclo(S-hy-S-Pro-S-Lue) (E6), cyclo(S-hy-R-Pro-S-Lue) (E7), and cyclo(S-Pro-Gly) (E8) together with 2 indole derivatives, indole-3-aldehyde (E9) and indole-3-acetic acid (E10). In accordance with those purified metabolites, only indole derivatives demonstrated remarkable bioactivity against tested microbes. A docking study on two different virulence proteins showed that E9 and E10 actively bind and interact with virulence proteins, assuring their ability to decrease microbial growth. In conclusion, the identified indole derivatives exhibited promising anti-biofilm and anti-virulence properties, suggesting potential for antibiotic development.

Indroduction COVID-19 is a contagious illness caused by the virus SARS-CoV-2, a major cause of death globally, even with effective vaccinations. Additionally, multidrug resistant bacterial and fungal pathogens are a real threat to many healthcare settings. Sinapic acid (SA), isolated from different plants or marine algae, has been reported to have antioxidant, antibacterial, and antiviral properties. Although there is evidence that SA has anti-SARS-CoV-2 activity, it is poorly absorbed when taken orally due to its intestinal metabolism. The current study aimed to improve SA's activity against SARS-CoV-2, different bacterial and fungal pathogens, bioavailability, and targeting using a nebulized, freeze-dried, transferosomal formulation.Methods A response-surface experimental study using phospholipid, cholesterol, and surfactants was employed to develop transferosomes. Various formulations were prepared and characterized for entrapment efficiency (EE), release, and size to select the optimized formulation. It was then lyophilized into a powder to be evaluated in vivo for its pharmacokinetic properties.Results and discussion SA exhibited antibacterial and antifungal activity, with SA-protransferosomes showing enhanced effectiveness compared to that of pure SA and approaching the efficacy of positive controls. Notably, SA protransferosomes demonstrated activity comparable to that of ciprofloxacin against E. faecalis and S. mutans and were effective against Candida albicans and Aspergillus niger, similar to nystatin. The optimized formula significantly enhanced the SARS-CoV-2 activity (IC50 = 0.016 +/- 0.008 mu g/mL), Cmax by 2.27 times, and AUC (0-infinity) by 5.4 times, as compared to pure SA. As a result, the use of nebulized SA-transferosomes can be regarded as a safe and efficient strategy to counter different infections.

Tamarix sp., often known as tamarisk, is a wide genus of flowering plants that reduce inflammation and cure wounds. In addition, using honey for wound therapy and care dates back thousands of years. Herein, we aimed to assess the wound healing potential of Saudi Tamarix honey (STH) metabolites in vivo, and support our hypothesis through in silico studies. Using an excision wound model, the possibility of Tamarix honey for in vivo wound healing was investigated via examining its effects on molecular targets involved in wound healing, including TGF-β, VEGF, matrix metalloproteinase-1 (MMP-1), TNF-α, and IL-1β. In addition, physicochemical properties were examined, and 1H NMR based metabolomics technique was employed to identify STH chemical metabolites. Results revealed that Tamarix honey had a substantial impact on wound closure rate, increased levels of TGF-β and VEGF, and markedly decreased the gene expression of MMP-1, TNF-α, and IL-1β compared to the group treated with topical MEBO ointment. Biochemical and histological studies corroborated the phenotypic results. Furthermore, the effect of Tamarix honey on the redox state of wounds was investigated. On the other hand, the physical and chemical properties of STH demonstrated that it possesses moisture content 14.60%, glucose 33.7%, fructose 37.9%, sucrose 5.0%, pH 5.0, hydroxymethylfurfural (HMF) 15.40 mg/kg, and diastase enzyme 17.6 Goth scale Min, all of which that attest to its superior quality and compliance with both national and international requirements. 1H NMR based metabolomics analysis revealed thirteen metabolites, mainly flavonoids. All Tamarix honey-derived flavonoids demonstrated high target probability against two wound healing-related targets, namely, glycogen synthase kinase-3β (GSK-3β) and NADPH oxidase 4 (NOX4). Alternatively, Tamarix honey-derived chlorogenic acid showed a high probability of targeting MMP-2, which was verified by molecular docking and molecular dynamics simulation (MDS). Our study highlights the potential of Tamarix honey in wound repair by revealing the most likely signaling pathway utilizing in silico and gene expression analysis.

OBJECTIVE:This study aims to assess the antibacterial potential of kojic acid produced by Trichoderma harzianum, a fungus isolated from the River Nile, and its potential application as a natural food preservative against Listeria monocytogenes. METHODS:A comprehensive chemical analysis of the ethyl acetate extract of T. harzianum was conducted using chromatographic and spectroscopic techniques. The isolated compounds were subsequently evaluated for their antibacterial activity and cytotoxic effects. RESULTS:Three major secondary metabolites were identified and purified from T. harzianum: kojic acid, di-(2-ethylhexyl) phthalate, and phomaligol A. Among these, only kojic acid demonstrated moderate antibacterial activity against L. monocytogenes, with negligible cytotoxicity against liver and colorectal cancer cell lines (IC50: 41.34 ± 1.7 μM and 17.35 ± 0.8 μM, respectively). In situ studies revealed a dose-dependent antibacterial effect of kojic acid against L. monocytogenes in skimmed milk. Further evaluation across different dairy products indicated that its efficacy was influenced by fat content, leading to a bacterial count reduction of up to 4.17 log units. Additionally, kojic acid effectively inhibited bacterial growth under both low and high contamination levels. Notably, it preserved milk stored at room temperature by preventing bacterial overgrowth for up to four days. CONCLUSION:These findings suggest that kojic acid possesses significant potential as a natural milk preservative due to its selective antibacterial activity against L. monocytogenes and favorable safety profile. As a result, kojic acid could serve as a viable alternative to synthetic chemical preservatives in dairy products.

This study assessed the in vitro anti-diabetic potential and bioactive constituents of ten Sri Lankan medicinal herbs. Initial screening of aqueous extracts for starch-digesting enzyme inhibition prioritised three plants with notable activity (p ≤ 0.05), for further assessment using methanolic extracts: Phyllanthus emblica (PE), Cassia auriculata (CA), and Hemidesmus indicus (HI). The selected plants were tested for starch-digesting enzyme inhibition, cytotoxicity, and bioactive metabolite identification, with PE subjected to GC-MS and LC-HRMS analyses. All three extracts contained alkaloids, flavonoids, tannins, and terpenoids, except saponins and steroids in PE. GC-MS analysis of PE annotated ten compounds, eight with anti-diabetic properties, while LC-HRMS annotated thirty metabolites, including fourteen anti-diabetic compounds. Cell viability assessments confirmed the non-toxic nature of PE, CA, and HI. The significant enzyme inhibition and non-toxic nature of PE highlight its potential to treat type 2 diabetes. Further in vivo and clinical studies are essential to determining effective dosage and toxicity levels.

In this study, we prepared silver nanoparticles (AgNPs) using the chemical reduction method. The structure and uniformity of the prepared AgNPs were confirmed using different characterization techniques, including XRD, SEM, FTIR, UV-Vis spectroscopy, zeta potential, and DLS. The antibacterial and antibiofilm testing of the prepared AgNPs revealed excellent potential against Escherichia coli and Klebsiella pneumoniae (MIC = 37.5 and 18.75 mu g/mL, respectively), Pseudomonas aeruginosa, and Candida albicans (percent of biofilm inhibition = 43% and 50%, respectively). Further, their mode of action was putatively elucidated by molecular dynamics simulations (MDS), which revealed that the desorbed Ag atoms could bind with and probably inhibit the bacterial GSH reductase, resulting in fatal increased oxidative stress inside the bacterial cell. To the best of our knowledge, this is the first comprehensive MDS work that uncovers the plausible mechanism of the bacterial GSH reductase inhibition by Ag atoms. Accordingly, we believe that the results presented herein will pave the way for additional research into metal-protein interactions, which will aid in the development of new metal-based treatments. Furthermore, the photocatalytic behavior of the prepared AgNPs was examined against methylene blue dye, and the results revealed optimistic efficiency as the removal percent exceeded 97% within 40 min with pseudo-first-order reaction kinetics.

Expansion of the microbial drug discovery pipeline has been impeded by a limited and skewed appreciation of the microbial world and its full chemical capabilities and by an inability to induce silent biosynthetic gene clusters (BGCs). Typically, these silent genes are not expressed under standard laboratory conditions, instead requiring particular interventions to activate them. Genetic, physical, and chemical strategies have been employed to trigger these BGCs, and some have resulted in the induction of novel secondary metabolites. This review encompasses a wide range of literature and emphasizes selected successful induction of microbial secondary metabolites examples through unconventional approaches such as quorum sensing, epigenetic modulation, and ribosome engineering. Whenever applicable, we will also discuss their mechanisms and optimizations to improve the microbial drug discovery process.

BackgroundHoney's medical values have been extensively recorded in literature. Yemeni Sidr honey was reported to treat many ailments like stomach and respiratory disorders. ESKAPE and other multidrug-resistant pathogens are considered one of the top three risks to global public health, so alternative strategies become critical demand against such pathogens or their biofilms. The current study aimed to explore the antibacterial and antioxidant potential of the Yemeni Sidr honey extracts. The antibacterial activity of the two Yemeni Sidr honey extracts (ST and SM) was assessed against different pathogenic strains. The antioxidant activity was also evaluated using ORAC, ABST, 5-LOX, and DPPH. Furthermore, 2D HSQC data of both ST and SM honey extracts were collected uploaded to the SMART platform to identify the possible metabolites in these extracts. The identified metabolites were analyzed using docking and molecular dynamic simulations (MDS) to identify the key players in the antibacterial action.ResultsThe antibacterial activity revealed that ST and SM extracts have similar activity against all tested pathogens. ST extract exhibited superior antibiofilm effect against P. aeruginosa and C. albicans by 68.2% and 62.6%, respectively, exceeding the reference standards. Moreover, ST extract displayed the highest antioxidant power against all assays except the DPPH assay. SMART dereplication of the HSQC data of ST extract revealed the annotations of five carbohydrates (fructose, glucose, mannose, maltose, and sucrose); while, SM extract showed three major phenolic compounds (chrysin, ellagic acid, and caffeic acid), in which chrysin and ellagic acid were likely the key players in the antibacterial action, based on MDS.ConclusionsThe study confirmed the effectiveness of Sidr honey against the tested multidrug-resistant pathogens. Additionally, our observations shed the light on the main secondary constituents in Yemini Sidr honey extracts, and their effective role in multidrug-resistant pathogens growth inhibition.

Pseudomonas aeruginosa (PA) is a critical pathogen, and its antibiotic resistance is largely driven by the quorum-sensing regulator LasR. Herein, we report the design, synthesis, and characterization of Aqs1C, a mutated peptide derivative of Aqs1, optimized to inhibit LasR and its quorum-sensing pathway. By introducing a targeted mutation, Aqs1C exhibited enhanced stability and binding affinity for LasR protein compared to its predecessor, Aqs1B. Using molecular dynamics simulations (MDS), the Aqs1C-LasR complex demonstrated a marked increase in structural stability, reflected in reduced root mean square deviation (RMSD) values and lower binding free energy. Electrostatic complementarity analysis showed stronger and more favorable interactions between Aqs1C and LasR. Further, GaMD experiments were able to reproduce the binding state between Aqs1C and LasR, indicating the binding mechanism between them. These molecular insights correlated with functional in vitro assays. Aqs1C effectively inhibited quorum-sensing-associated virulence factors in PA, involving biofilm formation (77.6 % inhibition), pyocyanin production (75.7 % inhibition), protease secretion (61.1 % inhibition), and rhamnolipid production (74.1 % inhibition), at a 100 μg/mL concentration, in a comparable or superior pattern to azithromycin (AZM). Molecular modelling, MDS, and GaMD insights and in vitro assays established Aqs1C as a promising candidate for therapeutic development to mitigate PA infections through targeted quorum-sensing disruption.

Titanium dioxide nanoparticles (TiO2 NPs) have attracted significant attention for their unique physicochemical features and various applications. This study demonstrated the biosynthesis of TiO2 NPs using Aspergillus fungal extract that served as a green and eco-friendly reducing and stabilizing agent. The biosynthesized nanoparticles were analyzed using SEM and TEM to determine their morphology, size, and distribution, FTIR to determine functional groups, and Zeta potential to assess their surface charge and stability. An extensive review of the Protein Data Bank (PDB) and literature indicated that TiO2 could target various cancer-relevant matrix metalloproteinases. In vitro screening indicated promising anticancer effects against the MCF7 breast cancer cell line. To investigate the possible mode of action of TiO2 NPs as an anticancer agent, human matrix metalloproteinase-3 was highlighted as a protein inhibited by metallic ions like PtCl2. Therefore, we investigated whether TiO2 could similarly interact with the active site of MMP-3. We hypothesized that TiO2 could interact with the MMP-3 active site and replace PtCl2 with modelled TiO2 in its co-crystallized binding site. A 100 ns-long MDS, binding free energy (Delta GBinding) of PtCl2 and TiO2 within MMP-3 binding site indicated that TiO2's enhanced binding affinity and stability, as evidenced by a Delta GBinding of-7.23 kcal/mol and average RMSD of 0.89 & Aring;, compared to PtCl2's lower affinity. In conclusion, endophytic fungi can be used efficiently in the biosynthesis of nanoparticles. Our study indicated TiO2 NPs have a potential anticancer effect, suggesting TiO2 binds to MMP3, potentially offering comparable inhibitory effects on the enzyme's activity.