Taoufiq Benali

This study aimed to investigate the antioxidant, antidiabetic, anticholinesterase, dermatoprotective effects, and antimicrobial properties of carvone, thymol and camphor. The antioxidant activity of these monoterpenes was performed by six methods: DPPH, FRAP, CUPRAC, MAC, PBD, and ABTS. The antidiabetic potential was assessed through the inhibition of both α ‐amylase and α ‐glucosidase; the inhibition of tyrosinase was assessed to study the dermatoprotective properties, while the antimicrobial efficiency was assessed based on both the agar well diffusion and the microtitration methods. Additionally, in silico investigations combining both molecular docking and dynamics (MD) simulations were conducted to explain the main findings. Thymol demonstrates the highest antioxidant capacity in four of the six assays (FRAP, CUPRAC, ABTS and DPPH). Carvone presents a mechanistically distinct antioxidant profile from thymol, excelling in metal chelation (MAC) and total reducing capacity (PBD), which represents the most scientifically noteworthy finding among the six assays. The three compounds significantly inhibited tyrosinase, with carvone displaying the highest effect (32.518 ± 4.419 mg KAE/g). A notable efficacy against BChE was exhibited; however, no compound inhibited the AChE enzyme. Moreover, modest inhibition of α ‐amylase was recorded while thymol and camphor exhibited a modest effect on α ‐glucosidase, with comparable values (1.432 ± 0.023 and 1.431 ± 0.025 mM ACAE/g, respectively). In addition, carvone has been shown to be highly effective with a bactericidal effect against P. aeruginosa , L. monocytogenes , E. coli and S. aureus , whereas thymol and camphor did not show any effect on the four bacterial strains, whereas no anticandidal effect was reported. Molecular docking demonstrated that carvone, thymol and camphor occupied the active site of the examined enzymes via different interactions, while MD simulation helped to corroborate the in vitro findings. Furthermore, ADMET prediction indicated that carvone, thymol and camphor had favourable ADMET profiles. In summary, carvone, thymol, and camphor may be promising as tyrosinase and α ‐glucosidase inhibitors and/or as lead compounds for developing new semisynthetic drugs for treating diabetes and pigmentation disorders.

Celtis australis L. was selected for investigation due to its traditional medicinal use and the limited number of studies available, particularly concerning its anticancer potential. This study examined the phenolic composition, the antioxidant activity, and the anticancer effects of methanolic, ethanolic, and aqueous extracts of C. australis L. The in vitro cytotoxic efficacy was assessed with the MTT assay on six tumor cell lines (HeLa, MV4‐11, OCI‐AML3, DAOY, OSN‐76, and U‐138‐MG) and two non‐cancerous cell lines (HEK293T and hCMEC/D3). C. australis L. extracts exhibited moderate antioxidant activity, as evidenced by their high IC ₅₀ values (110–436 μg/mL). The FRAP reducing power was low (2.09–6.24 mg AAE/g), and the aqueous extract was least active, with IC ₅₀ values ranging from 152 to 207 μg/mL in the ABTS assay. The HPLC‐ESI‐MS/MS analysis indicated that the extracts contain a variety of phenolic compounds dominated by neochlorogenic acid, chlorogenic acid, procyanidin B2, (−)‐epicatechin, isoquercitrin, rutin, phloretin, and delphindin‐3,5‐diglucoside. Cytotoxicity assays demonstrated a dose‐dependent reduction in cell viability, with DAOY cells exhibiting the highest sensitivity. Water extract exhibited significant inhibitory effects at elevated concentrations, whereas ethanol extract showed greater potency at intermediate doses (7.5%–50%) for specific cancer cell lines. Methanol extract exhibited a more gradual impact and showed reduced potency at elevated doses. According to IC ₅₀ values, the ethanolic extract was the most efficacious in four out of the six cancer cell lines, whereas water extract demonstrated notable potency for OCI‐AML3 and OSN‐76 but were less effective on normal cells, suggesting selectivity based on cell type. The selectivity index indicated that methanol exhibited the highest selectivity, especially against OSN‐76, MV4‐11, OCI‐AML3, and HeLa cell lines, implying its predilection for cancer cells over normal cells. Ethanol demonstrated notable selectivity, particularly toward OSN‐76 and MV4‐11. Conversely, water extracts exhibited minimal selectivity across all strains. In summary, methanol and ethanol extracts demonstrate the best potential for selective anticancer efficacy.

Micromeria graeca L. is an aromatic plant rich in bioactive molecules with potential antimicrobial properties. This study evaluated the antibacterial activity of extracts obtained using different solvents and extraction techniques. Among the tested samples, the methanolic ultrasound‐assisted extract (MGME‐UAE) exhibited the strongest bactericidal effect, selectively inhibiting Proteus mirabilis (inhibition zone 12.7 ± 0.6 mm; minimum inhibitory concentration [MIC] = 6.25 mg/mL). Liquid chromatography coupled with photodiode‐array and electrospray ionization–mass spectrometry (LC–PDA/ESI–MS) profiling revealed sagerinic acid (30.37 ± 0.70 mg/g), 5‐caffeoylquinic acid, and caffeic acid as major constituents. Mechanistic assays showed that MGME‐UAE increased membrane permeability, causing significant leakage of DNA/RNA and proteins, which was further confirmed by scanning electron microscopy (SEM) visualization of cell wall disruption. These findings highlight M. graeca as a promising source of natural antibacterial agents, particularly against P. mirabilis .

Candida albicans ( C. albicans ) is an opportunistic yeast that forms biofilms, which confer increased resistance to antifungal agents, making infections very difficult to treat. One of the mechanisms regulating this virulence is quorum sensing (QS), which can be defined as a cellular communication mechanism based on the production of autoinducer, namely, farnesol. We previously reported that the essential oils of Cistus ladanifer , Matricaria chamomilla , and Pistacia lentiscus inhibit C. albicans . In this context, a virtual screening of 48 molecules derived from these plants, as well as their ADMET property predictions, was undertaken to identify the most promising ligands for inhibiting QS receptors (CYC and RAS1) compared to farnesol. The latter exhibited a binding affinity of −7.0 kcal/mol for both CYC and RAS1. Two phytomolecules, namely, chamazulene and γ ‐muurolene, exhibited stronger binding affinities of −7.6 and −8.1 kcal/mol, respectively, for CYC, while toward the RAS1 receptor, they showed identical binding affinities of −7.1 kcal/mol. According to the binding free energy calculations performed using Prime MM‐GBSA, the complexes formed by γ ‐muurolene exhibited high stability, maintained by coulombic, lipophilic, and Van der Waals interactions, demonstrating that γ ‐muurolene is a promising inhibitor of QS. Molecular dynamic simulations confirmed the conformational stability of the CYC‐ γ ‐muurolene and RAS1‐ γ ‐muurolene complexes, characterized by low RMSD values, suggesting favorable dynamic behavior. The results as a whole provide a solid foundation for further experimental validation.

Cinnamaldehyde, a bioactive compound derived from cinnamon plants, has demonstrated various biological capacities, i.e., antimicrobial, antidiabetic, antiobesity, and anticancer efficiencies. Here, the potential antioxidant, anticholinesterase, anti‐α‐amylase, anti‐α‐glucosidase, and antityrosinase activities of cinnamaldehyde were investigated by combining in vitro assays and in silico approach based on molecular docking and MD simulations to elucidate the obtained effects. The main results indicated that cinnamaldehyde exhibited promising antioxidant activity and effectively inhibited acetylcholinesterase (4.935 ± 0.060 mg GALAE/g), butyrylcholinesterase (1.172 ± 0.023 mg GALAE/g), and tyrosinase (63.317 ± 5.511 mg KAE/g) enzymes. Molecular docking and MD simulations revealed that the interactions between cinnamaldehyde and these enzymes enhanced the stability of the formed complexes. Additionally, in silico ADME assessment indicated favorable profiles. Overall, these results suggest that cinnamaldehyde holds potential as an inhibitor of cholinesterases and tyrosinase enzymes, making it a promising lead compound for the design of semisynthetic drugs to manage issues like Alzheimer’s and pigmentation disorders.

The rising prevalence of chronic diseases and antibiotic-resistant bacteria underscores the need for natural remedies as sustainable, side-effect-free alternatives. This study highlights the therapeutic potential of carob, a plant rich in bioactive compounds with remarkable health benefits. Aqueous extracts from its leaves and pods contain significant levels of polyphenols (9.2 ± 0.31 to 8.53 ± 0.32 mg GAE/g), flavonoids (up to 3.34 ± 0.14 mg QE/g), and tannins (4.34 ± 0.32 to 0.39 ± 0.06 mg EC/g), contributing to its strong antioxidant properties. Furthermore, carob extract exhibited potent antibacterial activity, with inhibition zones measuring 8.2 ± 0.5 mm for Salmonella spp., 8.4 ± 0.6 mm for Staphylococcus aureus, 9.5 ± 0.5 mm for Escherichia coli, and 8.8 ± 0.6 mm for Bacillus cereus. These bioactive compounds support gut health by acting as antioxidants and microbiome regulators, preventing inflammatory bowel diseases and promoting intestinal balance. This study highlights carob's role in chronic disease prevention, advocating for a holistic health approach.

Among heavy metals, cadmium (Cd) is shown to have adverse consequences for plants. Due to its harmful nature and ability to move through the soil–plant system, it is a very worrying element for soil experts and plant physiologists. In this work, we designed a pot experiment to study the influence of three soil concentrations of cadmium (0, 15, and 30 mg/kg) to explore its physiological impacts, and its portioning in the whole plant of three hulless barley varieties. Our findings demonstrated marked Cd accumulation in roots, leaves, and stems under severe Cd stress (30 mg/kg). Cd stress was also shown to reduce photosynthetic activity, chlorophyll fluorescence (Fv/Fm), and transpiration rates (E). The application of Cd in the soil increased the activities of catalase (CAT), ascorbate peroxidase (APX), and guaiacol peroxidase (POD) enzymes, as well as the levels of oxidative stress markers such as malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and proline. These results reflect the negative effects of cadmium on morpho-physiological traits in barley genotypes. However, the principal component analysis indicated a significant correlation between oxidative stress indicators and enzymatic activities, along with different levels of Cd tolerance between Tombari, Assiya, and Giza 130 genotypes. When exposed to Cd, these varieties shifted a significant amount of energy from growth to produce antioxidant compounds and osmolytes. Despite this, these defenses did not effectively shield the plant from the detrimental effects of oxidative stress induced by Cd accumulation at vegetative stages. Consequently, we highly recommend testing these varieties under Cd-contaminated soil to investigate the rate of cadmium accumulation in the seeds, the harvested part used in human nutrition.

With the prohibition of many chemical pesticides due to their impact on the health of living resources, as well as on the quality of food, soil and water, it has become essential to look for alternatives of natural origin that promote sustainability. This study focuses on the antifungal activity of Rosmarinus officinalis, Origanum majorana and Citrus aurantium essential oils against Phytophthora palmivora and Alternaria alternata. The antifungal activity of six essential oil concentrations was tested in vitro by the direct contact method. After a seven-day follow-up, the results revealed a significant antifungal effect of Origanum majorana essential oil, with total inhibition of mycelial growth at a concentration of 1.5 μl/ml and 3.33 μl/ml on Phytophthora palmivora and Alternaria alternata respectively. While Rosmarinus officinalis and Citrus aurantium showed less antifungal activity, with MICs ranging from 6.66 μL/mL to 12.5 μL/mL. These promising results pave the way for in vivo efficacy tests to confirm its use in more sustainable agricultural practices.

In this paper, we report a highly regioselective 1,3-dipolar cycloaddition (1,3-DC) reaction of nitrilimines with thioaurone derivatives that afforded the hitherto unreported spiropyrazolines. Spectroscopic and spectrometric data were utilized to confirm the structure of all products and elucidate the reaction’s regiochemistry. A mechanistic study was performed within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) computational level to explain the regioselectivity observed. The electron localization function (ELF) topological analysis confirms the carbenoid-type (cb-type) mechanism of the cycloaddition reactions between nitrilimines and thioaurones. The intermolecular interactions between reagents in this reaction account for the regioselectivity observed experimentally.