1,3-Dipolar cycloaddition reactions of a sugar-based trifluoromethylated nitrone-to-maleimide and allyl bromide afforded a series of cycloadducts in good yield. The same nitrone reacts with propargyl ...acetate lead, after rearrangement of 4-isoxazoline, to aziridine with good yield. The obtained compounds were evaluated for their in vitro antimicrobial potency. Additionally, we are interested in predicting their physicochemical parameters such as lipophilicity and bioactivity score as well as their pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) such as plasma protein binding (PPB) penetration of the blood–brain barrier (BBB), human intestinal absorption (HIA), cellular permeability (PCaco-2), cell permeability of Madin–Darby canine kidney (PMDCK),
P
-glycoprotein (
P
-gp) efflux, CYP inducers, substrates and inhibitors’ skin and permeability (PS), and their toxicological behavior mutagenicity, carcinogenicity, acute, environmental, cardiotoxicity (hERG inhibition) using in silico computational methods. Also, we aimed to validate QSAR models for the elucidation of their antitarget using 32 sets of end-points (
IC
50
,
K
i
and
K
act
). The obtained result provides good information about the pharmacotherapy potential and toxicity of the examined molecules with good compliance between in vitro antimicrobial and the predicted properties. Findings indicated and encouraged the use of these compounds and their derivatives for further in vivo evaluations in the design and the elucidation of the intrinsic mechanisms as well as the efficacy of the selected powerful drug.
Graphic abstract
Herbs and spices have been used since antiquity for their nutritional and health properties, as well as in traditional remedies for the prevention and treatment of many diseases. Therefore, this ...study aims to perform a chemical analysis of both essential oils (EOs) from the seeds of Carum carvi (C. carvi) and Coriandrum sativum (C. sativum) and evaluate their antioxidant, antimicrobial, anti-acetylcholinesterase, and antidiabetic activities alone and in combination. Results showed that the EOs mainly constitute monoterpenes with γ-terpinene (31.03%), β-pinene (18.77%), p-cymene (17.16%), and carvone (12.20%) being the major components present in C. carvi EO and linalool (76.41%), γ-terpinene (5.35%), and α-pinene (4.44%) in C. sativum EO. In comparison to standards, statistical analysis revealed that C. carvi EO showed high and significantly different (p < 0.05) antioxidant activity than C. sativum EO, but lower than the mixture. Moreover, the mixture exhibited two-times greater ferric ion reducing antioxidant power (FRAP) (IC50 = 11.33 ± 1.53 mg/mL) and equipotent chelating power (IC50 = 31.33 ± 0.47 mg/mL) than the corresponding references, and also potent activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 19.00 ± 1.00 mg/mL), β-carotene (IC50 = 11.16 ± 0.84 mg/mL), and superoxide anion (IC50 = 10.33 ± 0.58 mg/mL) assays. Antimicrobial data revealed that single and mixture EOs were active against a panel of pathogenic microorganisms, and the mixture had the ability to kill more bacterial strains than each EO alone. Additionally, the anti-acetylcholinesterase and α-glucosidase inhibitory effect have been studied for the first time, highlighting the high inhibition effect of AChE by C. carvi (IC50 = 0.82 ± 0.05 mg/mL), and especially by C. sativum (IC50 = 0.68 ± 0.03 mg/mL), as well as the mixture (IC50 = 0.63 ± 0.02 mg/mL) compared to the reference drug, which are insignificantly different (p > 0.05). A high and equipotent antidiabetic activity was observed for the mixture (IC50 = 0.75 ± 0.15 mg/mL) when compared to the standard drug, acarbose, which is about nine times higher than each EO alone. Furthermore, pharmacokinetic analysis provides some useful insights into designing new drugs with favorable drug likeness and safety profiles based on a C. carvi and C. sativum EO mixture. In summary, the results of this study revealed that the combination of these EOs may be recommended for further food, therapeutic, and pharmaceutical applications, and can be utilized as medicine to inhibit several diseases.
This study aimed to investigate and compare the total phenolic content (TPC) and total flavonoid content (TFC) and antioxidant and antibacterial activities of different extracts recovered from Date ...Palm Pollen collected from Tunisian cultivars of Kerkennah (DPP-K) and Tozeur (DPP-T) using various solvents, including hexane, chloroform, ethyl acetate, acetone, ethanol and water. The results revealed that DPP-T had higher TPC than DPP-K for all solvent extracts, except for hexane, with a value of 237.74±9.58mg GAE/g for the water extract. The highest level of TFC (75.10±4.37mg QE/g) was recorded in the acetone DPP-T extract, which was about twice as high as that of DPP-K. A total of eight phenolic compounds were identified and quantified in both extracts by HPLC, namely gallic acid, catechin, caffeic acid, epicatechin, vanillic acid, coumarin, quercitin and rutin. The antioxidant activities of the extracts were screened using DPPH and β-carotene bleaching assays. The results indicated that the DPP-T acetone extract showed the best DPPH scavenging activity (IC50=46.56±0.28μg/ml), with no activity being recorded for DPP-K. The DPP-T extract also showed significant effects in terms of the β-carotene test (28.12±0.04μg/ml) when compared to BHT as a reference standard. The extracts were screened for antimicrobial activity against 10 bacterial and 7 fungal strains, and the results showed that ethyl acetate DPP-K extract exhibited the strongest activity against Listeria monocytogenes and that the Staphylococcus aureus strain was most sensitive to DPP-T, with MIC and MBC values of 0.98mg/ml and 1.95mg/ml, respectively. Both DPP-T and DPP-K showed strong inhibition effects on the growth of oxysporum. Further time kill assays demonstrated the potency of DPP-K and DPP-T ethyl acetate extracts to inhibit the growth of L. monocytogenes and S. aureus, respectively. Overall, the findings suggest that DPP could be considered a promising source of new natural antioxidant and antimicrobial agents for use in various food and pharmaceutical products and formulations. This suggested that the DPP extract is a good potential inhibitor of food spoiling microbial growth and could be a highly effective therapeutic choice for human and plant infections.
Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention ...and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured.
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A novel series of enantiopure isoxazolidines have been synthesized in good yields and with high stereoselectivity by 1,3-dipolar cycloaddition between a (–)-menthone-derived nitrone ...as a glycine equivalent and various terminal alkenes. The structures and the stereochemistry of the obtained cycloadducts have been determined by spectroscopic methods. Almost all the compounds were predicted to exhibit various degrees of antioxidant and antibacterial potentiality. Finally, the drug likeness and bioactivity were calculated using Molinspiration software. The results indicated that all compounds are in accordance with Lipinski’s rule of five showing good drug likeness and bioactivity score for drug targets with no violations.
For the first time, we reported the phytochemical composition of the volatile oil from Thymus musilii Velen (T. musilii). The antioxidant and antimicrobial activities against various food-borne and ...clinical pathogenic microorganisms were also tested. The thyme oil was particularly rich in thymol (67.697 ± 0.938%), and thymyl acetate (12.993 ± 0.221%). The strongest antioxidant activity of the essential oil was registered with the tests: ABTS (IC50 = 5.6 × 10−4 mg/mL) and β-carotene/linoleic acid (IC50 = 3.2 × 10−3 mg/mL). This thymol-chemotype oil was active against all microorganisms tested with an inhibition growth zone ranging from 21.33 ± 1.52 mm for Proteus mirabilis (P. mirabilis) to 37.33 ± 1.15 mm for Candida vaginalis (C. vaginalis) strain. Overall, the tested oil exhibited bactericidal and fungicidal activities and only a small quantity of the tested essential oil was found to be sufficient for inhibiting the growth of the tested microorganisms. Furthermore, molecular docking results implies that, among the bioactive compounds, β-caryophyllene interacted strongly with the active site residues of TyrRS, GLMS and Gyrase enzymes and consequently support our in vitro results with the highest inhibition potential of this essential oil against tested pathogens, especially Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Our results suggested that essential oil of T. musiliii exhibited strong biological activities with a promising source of various natural compounds.
Piper cubeba L. fruit is an important species used in folk medicine for different types of pains such as rheumatism, chills, flu, colds, muscular aches, and fever. This study examines the chemical ...constituents, antioxidant activity, and potential inhibitory effect against human peroxiredoxin 5, a key enzyme of P. cubeba essential oil from fruits. Using gas chromatography coupled with mass spectrometry (GC–MS), the principal components were methyleugenol (41.31%) and eugenol (33.95%), followed by (E)-caryophyllene (5.65%), p-cymene-8-ol (3.50%), 1,8-cineole (2.94%), and α-terpinolene (1.41%). Results showed similar scavenging activity via 2,2-diphenyl-1-picrylhydrazyl DPPH radical scavenging activity (IC50 = 110.00 ± 0.08 μg/mL), as well as very potent antioxidant activity against both ferric reducing/antioxidant power (FRAP) (106.00 ± 0.11 μg/mL) and β-carotene bleaching (IC50 = 315.00 ± 2.08 μg/mL) assays when compared to positive butylated hydroxytoluene and ascorbic acid. The molecular docking approach has also been performed to screen the antioxidant activities of the major and potent compounds against human protein target peroxiredoxin 5. Results showed good binding profiles and attributed the strongest inhibitory activity to β-caryophyllene oxide (–5.8 kcal/mol), followed respectively by isocembrol and α-selinene (–5.4 kcal/mol), and viridiflorol (–5.1 kcal/mol). Furthermore, ADME (absorption, distribution, metabolism and excretion)-related physicochemical and pharmacokinetic properties have been assessed and support our in vitro findings. This work demonstrates the powerful antioxidant potency of cubeba pepper and paves the way for the discovery and development of antioxidant agent with high potency.
Isoxazolidine derivatives were designed, synthesized, and characterized using different spectroscopic techniques and elemental analysis and then evaluated for their ability to inhibit both α-amylase ...and α-glucosidase enzymes to treat diabetes. All synthesized derivatives demonstrated a varying range of activity, with IC
values ranging from 53.03 ± 0.106 to 232.8 ± 0.517 μM (α-amylase) and from 94.33 ± 0.282 to 258.7 ± 0.521 μM (α-glucosidase), revealing their high potency compared to the reference drug, acarbose (IC
= 296.6 ± 0.825 µM and 780.4 ± 0.346 µM), respectively. Specifically, in vitro results revealed that compound
achieved the most inhibitory activity with IC
values of 5.59-fold and 8.27-fold, respectively, toward both enzymes, followed by
. Kinetic studies revealed that compound
inhibits both enzymes in a competitive mode. Based on the structure-activity relationship (SAR) study, it was concluded that various substitution patterns of the substituent(s) influenced the inhibitory activities of both enzymes. The server pkCSM was used to predict the pharmacokinetics and drug-likeness properties for
, which afforded good oral bioavailability. Additionally, compound
was subjected to molecular docking to gain insights into its binding mode interactions with the target enzymes. Moreover, via molecular dynamics (MD) simulation analysis, it maintained stability throughout 100 ns. This suggests that
possesses the potential to simultaneously target both enzymes effectively, making it advantageous for the development of antidiabetic medications.
, or star anise, has many uses ranging from culinary to religious. It has been used in the food industry since ancient times. The main purpose of this study was to determine the chemical composition, ...antibacterial, antibiofilm, and anti-quorum sensing activities of the essential oil (EO) obtained via hydro-distillation of the aerial parts of
. Twenty-four components were identified representing 92.55% of the analyzed essential oil. (
)-anethole (83.68%), limonene (3.19%), and α-pinene (0.71%) were the main constituents of
EO. The results show that the obtained EO was effective against eight bacterial strains to different degrees. Concerning the antibiofilm activity, trans-anethole was more effective against biofilm formation than the essential oil when tested using sub-inhibitory concentrations. The results of anti-swarming activity tested against
.
PAO1 revealed that
EO possesses more potent inhibitory effects on the swarming behavior of PAO1 when compared to trans-anethole, with the percentage reaching 38% at a concentration of 100 µg/mL. The ADME profiling of the identified phytocompounds confirmed their important pharmacokinetic and drug-likeness properties. The in silico study using a molecular docking approach revealed a high binding score between the identified compounds with known target enzymes involved in antibacterial and anti-quorum sensing (QS) activities. Overall, the obtained results suggest
EO to be a potentially good antimicrobial agent to prevent food contamination with foodborne pathogenic bacteria.
The main objectives of the present study were to investigate anti-
spp., antibiofilms, and anti-quorum-sensing (anti-QS) properties of caraway essential oil in relation to their phytochemical ...composition. The results obtained show the identification of twelve compounds, with carvone (58.2%) and limonene (38.5%) being the main ones. The obtained essential oil (EO) is particularly active against all
spp. species, with bacteriostatic action against all tested strains (MBC/MIC ratio ≥ 4) and with inhibition zones with high diameters of growth, ranging from 8.66 ± 0.58 mm for
ATCC 35016 to 37.33 ± 0.58 mm for
ATCC 17749. Caraway essential oil (Carvone/limonene chemotype) exhibits antioxidant activities by using four tests (DPPH = 15 ± 0.23 mg/mL; reducing power = 7.8 ± 0.01 mg/mL; β-carotene = 3.9 ± 0.025 mg/mL; chelating power = 6.8 ± 0.05 mg/mL). This oil is particularly able to prevent cell-to-cell communication by inhibiting swarming motility, production of elastase and protease in
PAO1, and violacein production in
in a concentration-dependent manner. A molecular docking approach shows good interaction of the identified bioactive molecules in caraway EO, with known target enzymes involved in antioxidant, antibacterial, and anti-QS activities having high binding energy. Overall, the obtained results highlight the possible use of caraway essential oil against pathogenic
species and to attenuate the secretion of virulence-related factors controlled by QS systems in Gram-negative bacteria. Therefore, this oil can be used by food industries to prevent biofilm formation on abiotic surfaces by
strains.