RETRACTED: Alminderej et al. Antimicrobial and Wound Healing Potential of a New Chemotype from Piper cubeba L. Essential Oil and In Silico Study on S. aureus tyrosyl-tRNA Synthetase Protein. Plants 2021, 10, 205.

The journal retracts the article, 'Antimicrobial and Wound Healing Potential of a New Chemotype from Piper cubeba L. Essential Oil and In Silico Study on S. aureus tyrosyl-tRNA Synthetase Protein' [...].

Antimicrobial and Wound Healing Potential of a New Chemotype from Piper cubeba L. Essential Oil and In Silico Study on S. aureus tyrosyl-tRNA Synthetase Protein.

Piper cubeba is an important plant commonly known as cubeb or Java pepper, and it is cultivated for its fruit and essential oils, largely used to treat various diseases. Up to today, there was no scientific report on wound healing activity. Thus, this study was initiated to evaluate for the first time the antimicrobial activity and wound healing potential of a new chemotype from Piper cubeba essential oil (PCEO) from fruits. Thirteen microbial strains have been selected to investigate the antimicrobial potential of PCEO. For the evaluation of the wound healing potential, sixteen rats were excised on the dorsal back and divided into four groups. The effect of PCEO on the malondialdehyde (MDA) and superoxide dismutase (SOD) activities in the healed wound area of rats and the biochemical parameters and skin histological analysis were also assessed. Results: Data showed that PCEO exhibited a powerful antimicrobial potential especially against Listeria monocytogenes and Staphylococcus aureus. In addition, the topical application of PCEO cream appears to increase the SOD level, wound healing and contraction but reduced the MDA amount suggesting an impressive and a rapid cutaneous healing power. Additionally, histopathological analysis of the granulation tissue revealed that the derma is properly restored and arranged after treatment with PCEO. The docking analysis of PCEO constituents against S. aureus tyrosyl-tRNA synthetase enzyme showed binding energies values in the range of -7.2 to -4.8 kcal/mol. In conclusion, the topic use of PCEO healing cream showed significant effect in accelerating the healing process, which may be attributed to the synergetic effect of antioxidant and antimicrobial properties of PCEO volatile constituents, making it a relevant therapeutic agent for the management of wounds and therefore confirming the popular traditional uses of this plant.

Antioxidant Activities of a New Chemotype of Piper cubeba L. Fruit Essential Oil (Methyleugenol/Eugenol): In Silico Molecular Docking and ADMET Studies.

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 ß-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 ß-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.

Synthesis and SPAR exploration of new semicarbazone-triazole hybrids in search of potent antioxidant, antibacterial and antifungal agents.

A new series of semicarbazone-triazole hybrid derivatives have been synthesized by condensation between heterocyclic aldehydes and the commercial semicarbazide hydrochloride. The in vitro antioxidant activity of these species was tested using 1,1-diphenyl-2-picrylhydrazyl radical, 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and Ferric reducing antioxidant power assays and their antimicrobial activity against different microbial strains was carried out. Furthermore, molecular properties prediction and drug likeness were also determinated using Molinspiration. Among such derivatives, compounds (E)-2-(4-((1-(2,6-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methoxy)benzylidene)hydrazine carboxamide (4c), and (E)-2-(4-((1-(2-methoxyphenyl)-1-H-1,2,3-triazol-4-yl)methoxy)benzylidene)hydrazine-carboxamide (4e) exhibit excellent scavenging ability, especially with IC50 = 1.57 ± 1.66 mg/mL (4c) and IC50 = 1.82 ± 0.15 mg/mL (4e) with 1,1-diphenyl-2-picrylhydrazyl radical and IC50 = 1.90 ± 1.33 mg/mL (4c) with 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) as compared to the standards butylhydroxytoluene (IC50 = 1.60 ± 1.98 mg/mL) and Trolox (IC50 = 1.45 ± 1.33 mg/mL), respectively. The antimicrobial assay results, show that compounds 4c and 4e highlighted the most interesting profile with the potent activity was obtained against S. enteritidis (1.56-fold) and then M. luteus (1.45-fold) which are significantly higher than the positive control, chloramphenicol. By the other hand, the synthesized semicarbazone derivatives met the Lipinski's rule criteria by presenting good drug likeness and bioactivity scores. The structure-property-activity relationships have been carried out in order to determine the effect of various substituents on the molecular and the biological properties. All these investigations confirm that our synthetic semicarbazone can be explored for generating new potential drug with good oral bioavailability.

Anti-microbial screening and cytotoxic activity of aerial part of Thymelaea hirsuta L. essential oil growing in south-west Tunisia.

This study aimed to investigate the antimicrobial and cytotoxic activities of essential oil isolated by the hydro-distillation of aerial parts of Thymelaea hirsuta. The antimicrobial activity of the oil was evaluated against eight bacterial and three fungal pathogenic strains. The results revealed that the essential oil exhibited a moderate-to-potent anti-microbial activity against all the microorganisms tested. Gram-positive bacteria were noted to be more sensitive to the oil than gram-negative bacteria and yeasts. In vitro cytotoxicity evaluation against HeLa cell lines showed that the essential oil exhibited moderate cytotoxicity on human tumor cells, with a high IC50 value of 175µg/mL. To the author's knowledge, this is the first study reporting on the antimicrobial and cytotoxic activities of Thymelaea hirsuta essential oil. Overall, the results indicate that the T. hirsuta essential oil has a number of attractive properties that might open new promising opportunities for the control or prevention of a wide range of microbial infections and cancers and can facilitate the use of essential oils as natural preservatives against spoilage microorganisms in food systems.

Stereoselective synthesis of enantiopure N-substituted pyrrolidin-2,5-dione derivatives by 1,3-dipolar cycloaddition and assessment of their in vitro antioxidant and antibacterial activities.

1,3-Dipolar cycloaddition between a chiral nitrone and N-substituted maleimides afforded unprecedented enantiopure spiro-fused heterocycles in good yields with a high enantio- and diastereoselectivity. The reaction was taking place on the less hindered face of the nitrone. The obtaining heterocycles were screened for their in vitro antioxidant properties and the results revealed that the potent antioxidant activity was generally recorded to compounds (3g) and (3e). The in vitro antibacterial activities of these two compounds were also investigated and the results demonstrated the strongest potential of compound (3g) against all the tested bacteria. Molecular properties were analyzed and showed good oral drug candidate like properties and that could be exploited as a potential antioxidant and antimicrobial agent. Finally, the preliminary results obtained from this investigation attempted to clarify if the structurally different side chains of active compounds interfere with their biological properties.

Lactococcus lactis is an Efficient Expression System for Mammalian Membrane Proteins Involved in Liver Detoxification, CYP3A4, and MGST1.

Despite the great importance of human membrane proteins involved in detoxification mechanisms, their wide use for biochemical approaches is still hampered by several technical difficulties considering eukaryotic protein expression in order to obtain the large amounts of protein required for functional and/or structural studies. Lactococcus lactis has emerged recently as an alternative heterologous expression system to Escherichia coli for proteins that are difficult to express. The aim of this work was to check its ability to express mammalian membrane proteins involved in liver detoxification, i.e., CYP3A4 and two isoforms of MGST1 (rat and human). Genes were cloned using two different strategies, i.e., classical or Gateway-compatible cloning, and we checked the possible influence of two affinity tags (6×-His-tag and Strep-tag II). Interestingly, all proteins could be successfully expressed in L. lactis at higher yields than those previously obtained for these proteins with classical expression systems (E. coli, Saccharomyces cerevisiae) or those of other eukaryotic membrane proteins expressed in L. lactis. In addition, rMGST1 was fairly active after expression in L. lactis. This study highlights L. lactis as an attractive system for efficient expression of mammalian detoxification membrane proteins at levels compatible with further functional and structural studies.

Kinetics of interaction between ADP-ribosylation factor-1 (Arf1) and the Sec7 domain of Arno guanine nucleotide exchange factor, modulation by allosteric factors, and the uncompetitive inhibitor brefeldin A.

The GDP/GTP nucleotide exchange of Arf1 is catalyzed by nucleotide exchange factors (GEF), such as Arno, which act through their catalytic Sec7 domain. This exchange is a complex mechanism that undergoes conformational changes and intermediate complex species involving several allosteric partners such as nucleotides, Mg(2+), and Sec7 domains. Using a surface plasmon resonance approach, we characterized the kinetic binding parameters for various intermediate complexes. We first confirmed that both GDP and GTP counteract equivalently to the free-nucleotide binary Arf1-Arno complex stability and revealed that Mg(2+) potentiates by a factor of 2 the allosteric effect of GDP. Then we explored the uncompetitive inhibitory mechanism of brefeldin A (BFA) that conducts to an abortive pentameric Arf1-Mg(2+)-GDP-BFA-Sec7 complex. With BFA, the association rate of the abortive complex is drastically reduced by a factor of 42, and by contrast, the 15-fold decrease of the dissociation rate concurs to stabilize the pentameric complex. These specific kinetic signatures have allowed distinguishing the level and nature as well as the fate in real time of formed complexes according to experimental conditions. Thus, we showed that in the presence of GDP, the BFA-resistant Sec7 domain of Arno can also associate to form a pentameric complex, which suggests that the uncompetitive inhibition by BFA and the nucleotide allosteric effect combine to stabilize such abortive complex.