Mabrouk Horchani

This study investigated the adaptive mechanisms of Shigella sonnei ATCC25931 in response to gamma irradiation stress (0.5 and 1 kGy), with a specific focus on the involvement of fatty acids (FAs) in membrane lipid composition remodeling, adherence, and extracellular proteins. The results demonstrated a notable enhancement in cell hydrophobicity and adherence to KB cells following irradiation, although the invasion rate exhibited a decline from 14% to 2.35% at 1 kGy. Furthermore, gamma irradiation induced notable alterations in fatty acid (FA) composition, characterized by a pronounced reduction in the unsaturated/saturated FA ratio. Additionally, the plasmid profiles revealed the loss of several original plasmids after gamma irradiation. The alterations in extracellular proteins were observed through SDS-PAGE, which demonstrated a reduction in expression at 1 kGy. Furthermore, a molecular docking analysis indicated that fatty acids play a role in inhibiting VirF, a key regulator of Shigella virulence. The least effective inhibitor was capric acid, while linoleic and gamma-linolenic acids formed the most stable inhibitory complexes, which prevented VirF from activating the virulence system. These alterations in fatty acids, plasmids, and extracellular proteins constitute adaptive responses to irradiation-induced stress.

Controlling the arbovirus vector Aedes aegypti represents a growing public health challange, intensifying the search for alternatives to combat the mosquito. In this context, the present study aims to evaluate the larvicidal activity of essential oils from three Piper species and their mixtures, as well as their preliminary toxicity and in silico acetylcholinesterase (AChE) inhibitory potential. The essential oils and mixtures were characterized by GC–MS. The larvicidal activity test was performed against third-stage larvae, and a preliminary toxicity test was preformed against Artemia salina. The results showed that the oils had a high content of phenylpropanoids such as safrole, dillapiole, and eugenol, as well as their derivatives. The mixtures showed lower toxicity when compared to the pure oils. P. aduncum oil showed the highest larvicidal action (LC₅₀ = 26.2 µg/mL), followed by P. callosum (LC₅₀ = 53.2 µg/mL), while P. divaricatum had the lowest activity (LC₅₀ = 123.8 µg/mL). Among the mixtures, the combination of P. divaricatum and P. aduncum stood out for its synergistic effect. Molecular docking analyses suggested that phytoconstituents interact favorably with AChE, supporting a neurotoxic mechanism associated with enzyme inhibition. Thus, Piper essential oils and mixtures are promising alternatives for the control of A. aegypti.

Background: This study investigated the effects of increasing levels of salinity on leaf phytochemical composition and the antioxidant, antidiabetic, and anti-obesity activities. Method: Three quinoa accessions grown under escalating NaCl treatments had their leaves exposed to various chemical analyses. Polyphenols, tannins, and flavonoids were among the phenolic substances whose concentrations were measured. The phenolic chemicals in the water extract were identified using HPLC-DAD-ESI-MS/MS. In vitro and in silico methods were used to measure anti-radical (DPPH), anti-alpha glucosidase, anti-alpha-amylase, and anti-lipase activities. Results: The results showed that water and ethanol, due to their polarity, were the most effective solvents for extracting phenolic compounds. Additionally, salt application led to a dose-dependent increase in total phenols (TPC), flavonoids (TFC), and tannins (CT) across all accessions. The accession DE-1 exhibited the highest contents with average values of 1453.03–4398.36 mg EGA/100 g DW, 322.7–1090.7 mg CAE/100 g DW, and 77.9–335.96 mg CAE/100 g DW of TPC, TFC, and Tannins, respectively. HPLC-ESI-DAD-MS/MS profiling of phenolic compounds led to identifying 18 constituents, including five major compounds (p-coumaric acid, caffeic acid, vanillic acid, p-coumaroyl hexose, and HHDP-galloyl glucose). Except for p-coumaroyl hexose and HHDP-galloyl glucose, which were extensively biosynthesized/accumulated in the salt-tolerant accession DE-1, the remaining phenolic compounds showed irregular evolution depending on accession and salt concentration. Moreover, ethanol and water extracts were evaluated for their anti-radical and enzyme-inhibitory activities. Conclusion: Salt-stressed DE-1 water extract showed strong antioxidant and enzyme inhibitory activities, indicating potential antidiabetic and anti-obesity effects. These activities were confirmed by in silico analysis.

Plants are a rich source of active metabolites that have been used to treat inflammation troubles. The current study aimed to identify the analgesic and anti-inflammatory compounds in Farsetia aegyptia and Zilla spinosa extracts. The anti-inflammatory activity was evaluated using the xylene-induced ear edema model in mice and the carrageenan-induced paw edema model in Wistar rats. Additionally, both central and peripheral analgesic effects were assessed in mice. The anti-lipoxygenase activity was examined through an in vitro enzyme inhibition assay. The phytochemical composition of the bioactive extracts was characterized using High-Resolution Liquid Chromatography–Mass Spectrometry (HR-LCMS). The aqueous extracts of both species exhibited the strongest anti-inflammatory activity. The F. aegyptia extract showed inhibition percentages of 51.82% at 6.25 mg/kg and 51.14% at 0.78 mg/kg, while the Z. spinosa extract yielded 65.05% inhibition at 12.5 mg/kg and 56.14% at 1.56 mg/kg in the paw and ear edema models, respectively. These extracts also demonstrated significant analgesic activity and inhibited lipoxygenase, with IC₅₀ values of 0.063 mg/mL for F. aegyptia and 0.072 mg/mL for Z. spinosa. HR-LCMS analysis revealed that the main constituent in Fa was malic acid (18.83%), while retronecine (19.03%) was the primary compound in Z. spinosa. Quercetin 3-[rhamnosyl-(1->2)-rhamnosyl-(1->6)-glucoside] was detected in both extracts with important proportions 7.87% in F. aegyptia and 8.29% in Z. spinosa and displayed the best docking score of −9.2 kcal/mol against the 5-lipoxygenase receptor (PDB: 3V99) in molecular docking studies. Overall, these findings indicate that F. aegyptia and Z. spinosa have significant potential as sources of novel anti-inflammatory agents.

Background/Objectives: Nucleoside precursors and derivatives play pivotal roles in the development of antimicrobial and antiviral therapeutics. The 2022 global outbreak of monkeypox (Mpox) across more than 100 nonendemic countries underscores the urgent need for novel antiviral agents. This study aimed to synthesize and evaluate a series of 5′-O-(palmitoyl) derivatives (compounds 2–6), incorporating various aliphatic and aromatic acyl groups, for their potential antimicrobial activities. Methods: The structures of the synthesized derivatives were confirmed through physicochemical, elemental, and spectroscopic techniques. In vitro antibacterial efficacy was assessed, including minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) determinations for the most active compounds (4 and 5). The antifungal activity was evaluated based on mycelial growth inhibition. Density functional theory (DFT) calculations were employed to investigate the electronic and structural properties, including the global reactivity, frontier molecular orbital (FMO), natural bond orbital (NBO), and molecular electrostatic potential (MEP). Molecular docking studies were conducted against the monkeypox virus and the Marburg virus. The top-performing compounds (3, 5, and 6) were further evaluated via 200 ns molecular dynamics (MD) simulations. ADMET predictions were performed to assess drug-likeness and pharmacokinetic properties. Results: Compounds 4 and 5 demonstrated remarkable antibacterial activity compared with the precursor molecule, while most derivatives inhibited fungal mycelial growth by up to 79%. Structure-activity relationship (SAR) analysis highlighted the enhanced antibacterial/antifungal efficacy with CH₃(CH₂)₁₀CO– and CH₃(CH₂)₁₂CO–acyl chains. In silico docking revealed that compounds 3, 5, and 6 had higher binding affinities than the other derivatives. MD simulations confirmed the stability of the protein-ligand complexes. ADMET analyses revealed favorable drug-like profiles for all the lead compounds. Conclusions: The synthesized compounds 3, 5, and 6 exhibit promising antimicrobial and antiviral activities. Supported by both in vitro assays and comprehensive in silico analyses, these derivatives have emerged as potential candidates for the development of novel therapeutics against bacterial, fungal, and viral infections, including monkeypox and Marburg viruses.

Citrus, which belongs to the Rutaceae family, is a very widespread genus in the Mediterranean Basin. In Tunisia, various parts of these spontaneous or cultivated plants are used in common dishes or in traditional medicine. The purpose of this work was to investigate C. limon and C. paradisi essential oil (EO). The samples were studied for their chemical composition using SPME/MS, as well as their antibacterial and antifungal activities. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) methods were used to evaluate the anticoagulant potentialities. The obtained results show that both essential oils are rich in monoterpenes hydrocarbons, whereby limonene is the main compound in C. paradisi EO (86.8%) and C. limon EO (60.6%). Moreover, C. paradisi EO contains β-pinene (13.3%), sabinene (2.2%) and α-pinene (2.1%). The antibacterial assay of the essential oils showed important bactericidal and fungicidal effects against all strains tested. In fact, the MICs values of C. limon EO ranged from 0.625 to 2.5 mg/mL against all Gram-positive and Gram-negative bacteria, and from 6.25 to 12.5 mg/mL for Candida spp. strains, while C. paradisi EO was more active against all bacteria with low MICs values ranging from 0.192 to 0.786 mg/mL, and about 1.5 mg/mL against Candida species. Both tested Citrus EOs exhibited interesting anticoagulant activities as compared to heparin. The molecular docking approach was used to study the binding affinity and molecular interactions of all identified compounds with active sites of cytidine deaminase from Klebsiella pneumoniae (PDB: 6K63) and the C (30) carotenoid dehydrosqualene synthase from Staphylococcus aureus (PDB: 2ZCQ). The obtained results show that limonene had the highest binding score of −4.6 kcal.mol⁻¹ with 6K63 enzyme, and −6.7 kcal.mol⁻¹ with 2ZCQ receptor. The ADME profiling of the major constituents confirmed their important pharmacokinetic and drug-like properties. Hence, the obtained results highlight the potential use of both C. limon and C. paradisi essential oils as sources of bioactive compounds with antibacterial, antifungal, and anti-coagulant activities.

As part of the valorization of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3β-hydroxyolean-12-en-28-oic acid, OA-1)-phtalimidines (isoindolinones) conjugates 18a–u bearing 1,2,3-triazole moieties were designed and synthesized by treating an azide 4 previously prepared from OA-1 isolated from olive pomace (Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues, 18a–u, were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes, and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa. Attractive results were obtained, notably against L. monocytogenes. Compounds 18d, 18g, and 18h exhibited the highest antibacterial activity when compared with OA-1 and other compounds in the series against tested pathogenic bacterial strains. A molecular docking study was performed to explore the binding mode of the most active derivatives into the active site of the ABC substrate-binding protein Lmo0181 from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor of the experimental data.