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The hydantoin scaffold is of substantial importance and it is commonly used in drug discovery. Herein, we report the synthesis of a novel phenytoine (a hydantoin derivative) with high yield by the reaction of phenytoin with 1-bromodecyl agent. Namely, 3-decyl-5,5- diphenylimidazolidine-2,4-dione (3DDID). The optimized geometry of the compound was calculated using density functional theory (DFT) method by B3LYP with 6-311++G(d,p) basis set. For this calculation, the X-ray data were used as initial values. Molecular electrostatic potential (MEP) surface and Frontier molecular orbitals (FOMs) were prepared for the compound. The crystal structure of the title compound contains intermolecular N-H···O, C-H···O hydrogen bonds and weak C-H···π interactions. Hirshfeld surface analysis and 2D fingerprint plots of the molecule aid comparison of intermolecular interactions and these analysis reveals that two close contacts are associated with intermolecular hydrogen bonds. The psychotropic activity evaluation of the synthesized compound was further explored using hole bored test for exploratory behaviors, dark//light box test for anxiolytic activity and Rota-road, traction, chimney testes were used to assess the myrelaxant effect. In addition, molecular modeling study was also conducted to rationalize the potential as neurotherapeutic drugs of our synthesized compound by predicting their binding modes, binding affinities and optimal orientation at the active site of the GABA-A receptor and Na+ channel. Finally, in silico ADMET predictions was also examined. HighlightsSynthesis, structural, and molecular characterization of a novel phenytoin derivative.DFT, XRD, and the Hirshfeld surface analysis of crystal structure was studied.Acute toxicity and psychotropic activity evaluation of 3-decyl-5,5 diphenylimidazolidine-2,4-dione (3DDID).Molecular modeling studies have been conducted to rationalize the obtained data and to determine the probable binding mode.Communicated by Ramaswamy H. Sarma.

This work is aimed the study of volatile compounds of Centauruim erythraea Raphin at three developmental stages (vegetative, flowering and post-flowering) and the investigation of their in vitro antioxidant, antidiabetic, dermatoprotective and antibacterial properties. The chemical composition of Centauruim erythraea essential oils (CEEO) was determined using GC/MS analysis. 39 volatile compounds were identified, belonging mainly to oxygenated monoterpenes, 51.63%, 44.10% and 53.69% at the vegetative, flowering and post-flowering stage, respectively. Menthol, carvacrol and tricosane were the main compounds of CEEO at the three developmental stages. The antioxidant effects of CEEO were determined by DPPH, FRAP and ABTS assays. CEEO at the flowering stage showed the best antioxidant effects by an IC50 = 47.18 ± 3.62 μg/mL, IC50 = 53.25 ± 2.19 μg/mL, IC50 = 65.34 ± 3.71 μg/mL determined by DPPH, FRAP and ABTS assays, respectively. The in vitro antidiabetic effect was evaluated by α-amylase and α-glucosidase enzymes inhibitory. CEEO at vegetative stage demonstrated a remarkable α-amylase (IC50 = 31.91 ± 0.336 μg/mL) and α-glucosidase (IC50 = 56.77 ± 1.02 μg/mL) inhibitory activities. Moreover, CEEO at the flowering and post-flowering stage strongly inhibited the tyrosinase enzyme with IC50 of 41.863 ± 0.031 μg/mL IC50 = 49.183 ± 0.298 μg/mL, respectively. The antibacterial effects were evaluated by determining the diameters of inhibition, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). CEEO showed important antibacterial inhibition at three seasonal stages and particularly against Staphylococcus aureus and Listeria monocytogenes. Moreover, CEEO at post-flowering stage presented bactericidal effects especially against S. aureus (MIC = MBC = 0.125% (v/v)), L. monocytogenes (MIC = MBC = 0.125% (v/v)), and Proteus mirabilis (MIC = MBC = 0.125% (v/v)). The results obtained in this study show that the biological properties of CEEO are mainly depending to phenological stages, during which volatile bioactive synthesis occurs.

Two new (4–5) and a known (3) derivatives of 1,2,4-triazolo [1,5-a]pyrimidine are synthesized and characterized through spectroscopic NMR, FT-IR and single crystal X-ray diffraction techniques. Along with experimental data, the predicted spectral data are obtained using density functional theory (DFT) at the B3LYP/6-31 + G (d,p) level of theory. The closest contacts between active atoms of the compounds are identified through Hirshfeld surface analysis and electrostatic potential map (EPM) studies. Relatively, good correlations were found between the experimental and predicted spectroscopic data with correlation coefficients higher than 90%. Hirshfeld surface analysis and EPM reveal that the closest interaction between the units of the compounds are between hydrogen atoms (39.6–46.3%). The antioxidant activity of 3–5 is evaluated using DPPH free radical scavenging and ferric reducing antioxidant power assays.

Despite the richness and biodiversity of invertebrates and algae in the Mediterranean Sea, these organisms are still poorly studied. The objective of our research is the discovery of bioactive lead compounds from the Mediterranean Sea sponge Hemimycale Collumella (HC). HC sponge (189.0 g) was collected from Mdiq costs on the Mediterranean Sea and extracted with methanol to yield (10 g) which was then subjected to fractionation. A bio-guided protocol was applied through evaluation of 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Oxygen Radical Absorbance Capacity (ORAC), α-amylase, β-glucosidase, pancreatic lipase inhibition as well as anti-collagenase, anti-elastase, antityrosinase and cytotoxic activity. 2,3-O-Hexahydroxydiphenoyl-(α/β)-glucose (1) and gentisic acid 2-O-β-glucoside (2) were isolated from the water fraction, quercetin-3-O-β-glucopyranoside (3), kaempferol 3-O-β-glucopyranoside (4) and isorhamnetin 3-O-β-glucopyranoside (5) from n-butanol fraction, gallic acid (6) from ethyl acetate fraction and gallic acid-3-methyl ether (7) from methylene chloride fraction. Compound 5 had the highest DPPH and ORAC activity. Compounds 1–5 had promising lipase inhibition activities which exceeded that of the standard Orlistat, while compounds 1–7 showed anti-tyrosinase activity higher than that of the standard Hydroquinone monomethyl ether. This is the first report for evaluation of the biological activities of 2, 3-O-hexahydroxydiphenoyl-(α/β)-glucose (1), gentisic acid 2-O-β-glucoside (2) and gallic acid-3-methyl ether (7).

Vitex agnus-castus is a medicinal plant of the Verbenaceae family, widely used in traditional medicine. This study is aimed at investigating the functional variability of phenolic compounds in different parts (leaves, stems, flowers, roots, and seeds) of Vitex agnus-castus methanolic extracts and at assessing their in vitro antidiabetic, antioxidant, and antibacterial activities. The results of HPLC-DAD-QTOF-MS indicated the presence of 25 phenolic compounds with a remarkable variability between plant parts; high levels were registered in chlorogenic, vanillic, 3,4-dihydroxybenzoic, and 3-hydroxybenzoic acids; hesperidin; and luteolin. V. agnus castus fruits and stems presented higher antioxidant activities. The extracts inhibited the growth of five pathogenic bacteria with MIC values documented between 7.81 and 31.25 mg/mL. In vitro antihyperglycemic effect revealed higher effect in flowers (2921.84 μg/mL) and seeds (2992.75 μg/mL) against α-glucosidase and of leaves (2156.80 μg/mL) and roots (2357.30 μg/mL) against α-amylase. The findings of this showed that V. agnus castus is a promising source for antidiabetic bioactive compounds. However, further investigations regarding the evaluation of in vivo antidiabetic effects of these compounds are needed.

This study evaluated firstly the performance of the Continuous Stirred Tank bioReactor system (CSTR) for the treatment of highly toxic petroleum refinery wastewaters at the pilot-scale. The reduction of the COD, BOD5, phenols, and the total petroleum hydrocarbon (TPH) reached 82.10%, 85.87%, 91.63%, and 81.11%, respectively at high hydraulic residence time (HRT = 10 days). Decreasing HRT to 5 and 2.5 days led to a decrease in the efficiency of the process and a decrease in biomass concentration was also observed (

Echinoderms have attracted the attention of scientists over the past few years after identifying a variety of unique structures endowed by interesting biological properties. However, the Moroccan coast biodiversity is still uninvestigated. In our ongoing attempts to valorize the rich Moroccan marine environment, this study aimed at assessing the antimicrobial activity of extracts obtained from three echinoderms Astropecten irregularis, Luidia sarsi and Ophiura albida against the human pathogens: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica and Bacillus subtilis. Moreover, their antioxidant activities were tested using standard methods in addition to the antidiabetic activity which has been evaluated in vitro against α-amylase and α-glucosidase enzymes. HPLC-DAD-QTOF-MS analysis revealed a significant content of some phenolic compounds such as pyrogallol, gallic, sinapic, ferulic, p-hydroxybenzoic and salicylic acids whose existence can be related to the endophytic fungi and/or dietary intake whereas GC-MS analysis exhibited diverse chemical structures such as cholesterol, oleic acid and glycerol 1-palmitate. Keywords: Echinoderms, Phenolic, α-Amylase, α-Glucosidase, Antimicrobial

Therapy combination is known for less side effects and higher efficacy. Essential oils (EOs) and mixture from two well-known plants (Syzygium aromaticum and Pelargonium graveolens) were tested for in vivo antioxidant and anti-inflammatory activities. The chemical analysis of the investigated Oils has lead to the identification of Eugenol (74.06%), Caryophyllene (11.52%) and Carvacrol acetate (7.82%) as the major element in S. aromaticum; while P. graveolens was much higher in Citronellol (30.77%), 10-epi-γ-Eudesmol (22.59%), and Geraniol (13.95%). In our pharmacological screening, both EOs demonstrated good antioxidant effects; especially S. aromaticum activity was much higher. In contrast, the in vivo investigation of the antioxidant activity using antioxidant enzymes (MDA, SOD and CAT) in the protozoa model (Tetrahemena pyriformis) demonstrated a higher protective effect of P. graveolens and EOs mixture. On the other hand, EOs demonstrated anti-inflammatory effect on the two phases of inflammation in the carrageenan induced edema model. Results from this study indicate that EOs from S. aromaticum and P. Graveolens can be used as a multitarget therapy.

A ring transformation of 6-methyl-7H[1,2,4]triazolo [4,3-b][1,2,4] triazepine-8(9H)-ones (thiones) in the presence of acetic anhydride give rise to a new series of 17 condensed 1,2,4-triazole derivatives (1–17). Plausible mechanisms are proposed and show the formation of a beta fused β-lactam moiety. The compounds were tested for their (i) inhibitory potential on digestive enzymes (α-amylase and α-glucosidase), and (ii) antioxidant activity using radical scavenging (DPPH and ABTS radicals) and ferric reducing power assays. The compounds showed interesting and promising antidiabetic activities compared to the reference drug Acarbose. Molecular docking study has been carried out to determine the binding mode interactions between these derivatives and the targeted enzymes. The results showed the strength of intermolecular hydrogen bonding in ligand-receptor complexes as an important descriptor in rationalizing the observed inhibition results. Moreover, molecular dynamics simulations are also performed for the best protein-ligand complex to understand the stability of small molecule in a protein environment. To shed light on the antioxidant activity of the synthesized compounds and the mechanism involved in DPPH free radical, DFT calculations were performed at the B3P86/6-311++G(d,p) level using the polarizable continuum model. The effect of aprotic solvent on bond dissociation enthalpies (BDEs) is investigated by calculating and comparing BDEs of 1 in methanol and dimethylsulfoxide as solvents using PCM. The obtained results show that the mechanism of action depends on the basic skeleton and the presence of substituted functional groups in these derivatives. BDEs are found to be slightly influenced by the aprotic solvent of less than 0.01 kcal/mol compared with those obtained in methanol.

The aim of this work is to deepen the pharmacological effect of 4-phenyl-1,5-benzodiazepin-2-one derivatives which have a similar structure to nonionic surfactants: 4-phenyl-1,5-benzodiazepin-2-one is the hydrophilic head, and the carbon chain is hydrophobic tail. The antinociceptive activity of 4-phenyl-1,5-benzodiazepin-2-one derivatives was determined using acetic acid-induced writhing and tail immersion tests. In addition, the in vitro antioxidant activities of the tested derivatives were determined by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method and ferric reducing power assay. A single oral administration of these compounds at the doses of 50 and 100 mg/kg significantly reduced the number of abdominal writhes induced by acetic acid injection. Acute pretreatment with 4-phenyl-1,5-benzodiazepin-2-one derivatives at the dose of 100 mg/kg caused a significant increase in the tail withdrawal latency in the tail immersion test. Additionally, a significant scavenging activity in DPPH and reducing power was observed in testing antioxidant assays. Finally, we carried out a study of the antioxidant activity of these derivatives. The results of this study reveal that these compounds have a low antioxidant activity compared to the BHT. It decreases with the polarity of the molecule. The present study suggests that 4-phenyl-1,5-benzodiazepin-2-one derivatives possess potent antinociceptive and antioxidant effects, which suggest that the tested compounds may be useful in the treatment of pain and oxidation disorders.

The aim of this study was the investigation of the in vitro antioxidant, antidiabetic, dermatoprotective, antidermatophyte, and antibacterial properties of Mentha viridis essential oil (MVEO). Chemical composition of MVEO was determined using GC-MS analysis. Antioxidant activity was estimated by three complementary methods: DPPH, FRAP and ABTS. The in vitro antidiabetic effect was evaluated by the inhibition of α-Amylase and α-Glucosidase. Inhibitory effects of tyrosinase and elastase were used to reveal the dermatoprotective property of MVEO. Antibacterial activity was tested against five strains using agar well diffusion assay and microtitration method. The chemical composition determination of MVEO revealed the presence of carvone (37.26), 1.8-Cineole (11.82), and Terpinen-4-ol (08.72%) as the main compounds. MVEO presented remarkable antioxidant effects by IC50 values of 80.45 ± 1.86 μg/mL, 101.78 ± 3.14 μg/mL, and 139.59 ± 3.12 μg/mL obtained by DPPH, FRAP and ABTS tests respectively. In vitro inhibition of enzymes implicated in hydrocarbures degradation showed that MVEO exhibited important inhibitory effects against α-Amylase (IC50 = 101.72 ± 1.86 μg/mL) and α-Glucosidase (IC50 = 86.93 ± 2.43 μg/mL). Moreover, MVEO demonstrated remarkable inhibition of tyrosinase (IC50 = 55.13 ± 1.01 μg/mL) and elastase (IC50 = 114.24 ± 1.22 μg/mL). The antifungal activity showed important inhibitions of three dermatophyte species (T. mentagrophytes, T. tonsurans and T. violaceum). The antibacterial activity showed an important bactericidal action against tested strains, especially, Staphylococcus aureus and Listeria monocytogenes (MIC = MBC = 0.25%). The findings of this work showed that volatile components of MVEO could constitute a new source for antioxidant, antidiabetic, dermatoprotective, antidermatophyte and antibacterial properties. However, further investigations regarding the isolation of MVEO main compounds and investigations of their biological properties are required.

Background Based on our previous ethnobotanical survey, the non-investigated Saharan plant Anabasis aretioides Coss. & Moq., growing in the region of Errachidia, was selected for pharmacological investigation. In Moroccan traditional medicine, A. aretioides is being used for diabetes treatment. Thus, the current work aims at evaluating the antidiabetic, antioxidant, and antibacterial activities of the plant in relation to the digestive tract. Methods The different parts of the plant (aerial parts, roots, seeds) were extracted with methanol (MeOH) and screened in enzymatic assays for their inhibitory potential against α-amylase and α-glucosidase, as well as antioxidant and antibacterial activities. Furthermore, the phenolic compounds were analyzed using HPLC-DAD-QTOF-MS. Results The MeOH extracts of A. aretioides aerial parts, roots, and seeds, respectively, inhibited α-amylase (IC50 of 3148.07 μg/mL, 2440.20 μg/mL, 3395.71 μg/mL) and α-glucosidase (IC50 of 2940.59 μg/mL, 3521.81 μg/mL, 3393.83 μg/mL). Moreover, compared to aerial parts and seeds, the plant roots exhibited higher antioxidant capacity and a potent reducing power. In resazurin microplate assay, the plant parts displayed a minimal inhibitory concentration (MIC) ranging from 7.81 mg/mL to 31.25 mg/mL. Chemical analysis revealed 25 phenolic compounds, with chlorogenic acid as the main phenolic compound in the aerial parts, hesperidin in roots, and quercitrin in seeds. Conclusion Anabasis aretioides cited for treatment of diabetes shows promising antioxidant and antibacterial properties, as well as an ability to inhibit digestive enzyme, including α-amylase and α-glucosidase. Thus, our results explain in part the traditional use of this Saharan medicine and open doors for further in vivo mechanistic and functional studies.

Scolymus hispanicus or the Golden Thistle, locally known as ‘Guernina’ or ‘Taghediwt’, is one of the most appreciated wild vegetables in Morocco. This study aims to characterise the functional chemical and pharmacological variability of Scolymus hispanicus parts (roots, stems, leaves and flowers). The chemical analysis revealed higher content of α-tocopherol in the flowers (2.79 ± 0.07 mg/100 g) and lead to the identification of 3 flavonoids and 13 phenolic acids, with high content of gallic acid in leaves (187.01 ± 10.19 mg/kg); chlorogenic (936.18 ± 92.66 mg/kg) and caffeic (4400.14 ± 191.43 mg/kg) acids in flowers, roots were much more higher in sinapic acid (0.25 ± 0.03 mg/kg) compared to the other parts. Moreover, Scolymus hispanicus ethanolic extracts exhibited interesting antioxidant and antimicrobial properties, promising anti-amylase and anti-glucosidase activities and relevant diuretic effect that confirms its traditional uses.

Hydro-distilled essential oil (EO) from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant capacity (TEAC) and Ferric-reducing antioxidant power assay (FRAP). The major identified compounds in GC/MS analysis were bornyl acetate (26.81%), camphor (22.40%) and α-pinene (7.16%), with 25 other minor constituents. No mortalities in acute toxicity were observed, indicating that the LD50 of T. articulata essential oil is highest than 5 g/kg. In the anti-inflammatory test based on chemical and mechanical induced trauma, the EO demonstrated an effective reduce swelling by 64.71 ± 9.38% and 69.09 ± 6.02% respectively obtained 6 h after administration at the dose of 200 mg/kg when compared to the control groups. Moreover in the antioxidant testing battery, T. articulata essential oil showed a promising scavenging effect measured by DPPH, TEAC and ferric-reducing power assays with IC50 values of 12.05 ± 0.24 mg/mL, 8.90 ± 0.17 mg/mL and 0.15 ± 0.01 mg/mL respectively. These results suggest that, the EO from the leaves of T. articulata constitutes a valuable source of anti-inflammatory and antioxidant metabolites. These findings argue for the possible integration of this oil in pharmaceutical, cosmetic and food industries., Graphical abstract

Objective. The aim of this work is to study and compare the antioxidant properties and phenolic contents of aqueous leaf extracts ofJuniperus thurifera,Juniperus oxycedrus,Juniperus Phoenicea,andTetraclinis articulatafrom Morocco.Methods. Antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging ability, Trolox equivalent antioxidant capacity (TEAC), and ferric reducing antioxidant power (FRAP) assays. Also the total phenolic and flavonoids contents of the extracts were determined spectrophotometrically.Results. All the extracts showed interesting antioxidant activities compared to the standard antioxidants (butylated hydroxytoluene (BHT), quercetin, and Trolox). The aqueous extract ofJuniperus oxycedrusshowed the highest antioxidant activity as measured by DPPH, TEAC, and FRAP assays with IC50values of17.91±0.37 μg/mL,19.80±0.55 μg/mL, and24.23±0.07 μg/mL, respectively. The strong correlation observed between antioxidant capacities and their total phenolic contents indicated that phenolic compounds were a major contributor to antioxidant properties of these plants extracts.Conclusion. These results suggest that the aqueous extracts ofJuniperus thurifera,Juniperus oxycedrus,Juniperus phoenicea,andTetraclinis articulatacan constitute a promising new source of natural compounds with antioxidants ability.

Tunisian untreated wastewater exhibits an average of 30 human helminth eggs per litre. After treatment, the concentration decreases to one egg per litre, or more in some cases. The percentage removal cited for wastewater processes provides no real indication of the destruction of the organisms, but merely of their transfer to another medium. In this study, we report the use of an environmentally friendly photoactive compound for wastewater disinfection. Photosensitization involves the generation of very toxic short-lived species on absorption of light by porphyrin. Microorganism photosensitization is potentially useful for sterilization and for the treatment of certain bacterial diseases. Gram-positive bacteria can be photoinactivated by a range of photosensitizers, but Gram-negative bacteria are not usually susceptible to photosensitized destruction. Our findings clearly demonstrate that the cationic meso-substituted porphyrin, tetra-(4-N-methyl-pyridyl) porphin tetra-tosylate (T4MPYP), is an efficient photosensitizer of helminth eggs on visible light illumination. The microscopic observation of helminth eggs shows that many types of ultrastructural alterations are potentially associated with exposure to T4MPYP and an adequate intensity of light: morphological changes without breakage; small alterations of eggshells; complete destruction. The degree of egg alteration increases with both increasing T4MPYP concentration and irradiation time. Moreover, the dissolved oxygen concentration, water quality and the type of eggs can influence the sensitivity of helminth eggs to photosensitization. Indeed, suspended solids (turbidity) were the most influential solution parameter on the efficiency of the photochemical process.