Tetraclinis articulata (Vahl) Mast. essential oil as a promising source of bioactive compounds with antimicrobial, antioxidant, anti-inflammatory and dermatoprotective properties: In vitro and in silico evidence.

Tetraclinis articulata is a known traditional medicinal plant used to manage various ailments, such as diabetes, rheumatism and infectious diseases. This study aims to determine the chemical constituents of T. articulata essential oil (EO) and to evaluate its in vitro antibacterial, anti-candidal, antioxidant, anti-inflammatory and dermatoprotective properties. In addition, a computational docking approach was used to predict the potential antioxidant, antibacterial, antifungal, anti-inflammatory, and cytotoxic properties of the identified compounds. The volatile oil obtained by hydrodistillation was characterized using gas chromatography-mass spectrometry (GC-MS). The antioxidant activity of T. articulata EO was investigated using three complementary assays: DPPH, ABTS and FRAP. Lipoxygenase (5-LOX) and tyrosinase enzymes were used to assess the anti-inflammatory and dermatoprotective effects of this oil. Moreover, disc-diffusion technique, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays were employed for the antimicrobial screening. The GC-MS analysis revealed that bornyl acetate (41.80 %), α-pinene (17.97 %) and camphor (15.97 %) are the major components of the studied EO. Moreover, T. articulata EO has exhibited promising antioxidant effect on FRAP, DPPH, and ABTS experiments. It also significantly inhibited 5-LOX (IC50 = 67.82 ± 0.03 µg/mL) and tyrosinase (IC50 = 211.93 ± 0.02 µg/mL). The results of MIC and MBC assays indicated that T. articulata EO is able to inhibit the growth of all tested bacteria (Gram + and Gram -) and Candida species. The ratio of tolerance level indicated that the tested oil was bactericidal against the Gram + bacteria and Candida species, whereas it has a bacteriostatic behavior against the Gram- bacteria. In light of these findings, T. articulata EO may be suggested as a potential pharmaceutical agent to prevent inflammation and skin problems and may serve as a natural antimicrobial and antioxidant alternative for sustainable application in food products.

Unveiling the Anti-Cholera and Active Diabetic Renoprotective Compounds of Maqian Essential Oil: A Computational and Molecular Dynamics Study.

Cholera is an exceptionally aggressive infectious disease characterized by the potential to induce acute, copious, watery diarrhea of considerable severity and renal inflammation. Diabetic nephropathy is a serious complication of diabetes mellitus that can lead to kidney failure through inflammation; thus, anti-inflammatory agents are promising therapies for diabetic nephropathy. Previous studies have shown that the essential oil of Zanthoxylum myriacanthum var. pubescens Huang, Maqian essential oil (MQEO), exhibits potent antibacterial, anti-inflammatory, and renoprotective activities in diabetic mice and has emerged as a potential therapeutic drug for the treatment of diabetic nephropathy complications. Therefore, the present study was carried out to screen the potential inhibition of cholera toxin and the diabetic renoprotective activity of MQEO through computational approaches. Twelve chemical constituents derived from MQEO were docked with cholera toxin and the target proteins involved in diabetic nephropathy, namely, TXNIP, Nrf2, and DPP IV, and, subsequently, the predictions of molecular dynamic simulations, the drug-likeness properties, and the ADMET properties were performed. α-terpineol showed high binding affinities toward the cholera toxin protein. For TXNIP, among all the chemical constituents, α-phellandrene and p-cymene showed strong binding affinities with the TXNIP protein and displayed relatively stable flexibility at the hinge regions of the protein, favorable physicochemical properties in the absence of hepatotoxicity, and low cytotoxicity. For Nrf2, α-terpineol exhibited the highest binding affinity and formed a very stable complex with Nrf2, which displayed high pharmacokinetic properties. All compounds had low free-binding energies when docked with the DPP IV protein, which suggests potent biological activity. In conclusion, based on a computational approach, our findings reveal that MQEO constituents have inhibitory activity against cholera toxin and are promising therapeutic agents for suppressing diabetic inflammation and for the treatment of diabetic nephropathy complications.

Exploring Cinnamoyl-Substituted Mannopyranosides: Synthesis, Evaluation of Antimicrobial Properties, and Molecular Docking Studies Targeting H5N1 Influenza A Virus.

The pursuit of innovative combinations for the development of novel antimicrobial and antiviral medications has garnered worldwide interest among scientists in recent times. Monosaccharides and their glycosides, such as methyl α-d-mannopyranoside derivatives, play a significant role in the potential treatment of viral respiratory pathologies. This study was undertaken to investigate and assess the synthesis and spectral characterization of methyl α-d-mannopyranoside derivatives 2-6, incorporating various aliphatic and aromatic groups. The investigation encompassed comprehensive in vitro antimicrobial screening, examination of physicochemical properties, molecular docking analysis, molecular dynamics simulations, and pharmacokinetic predictions. A unimolar one-step cinnamoylation reaction was employed under controlled conditions to produce methyl 6-O-cinnamoyl-α-d-mannopyranoside 2, demonstrating selectivity at the C-6 position. This represented a pivotal step in the development of potential antimicrobial derivatives based on methyl α-d-mannopyranoside. Subsequently, four additional methyl 6-O-cinnamoyl-α-d-mannopyranoside derivatives were synthesized with reasonably high yields. The chemical structures of these novel analogs were confirmed through a thorough analysis of their physicochemical properties, elemental composition, and spectroscopic data. In vitro antimicrobial assays were conducted against six bacterial strains and two fungal strains, revealing promising antifungal properties of these methyl α-d-mannopyranoside derivatives in comparison to their antibacterial activity. Moreover, cytotoxicity testing revealed that the compounds are less toxic. Further supporting these findings, molecular docking studies were performed against the H5N1 influenza A virus, indicating significant binding affinities and nonbonding interactions with the target protein 6VMZ. Notably, compounds 4 (-7.2) and 6 (-7.0) exhibited the highest binding affinities. Additionally, a 100 ns molecular dynamics simulation was conducted to assess the stability of the complex formed between the receptor 6VMZ and methyl α-d-mannopyranoside derivatives under in silico physiological conditions. The results revealed a stable conformation and binding pattern within the stimulating environment. In silico pharmacokinetic and toxicity assessments of the synthesized molecules were performed using Osiris software (version 2.9.1). Compounds 4 and 6 demonstrated favorable computational and pharmacological activities, albeit with a low drug score, possibly attributed to their higher molecular weight and irritancy. In conclusion, this study showcases the synthesis and evaluation of methyl α-d-mannopyranoside derivatives as promising candidates for antimicrobial and antifungal agents. Molecular docking and dynamics simulations, along with pharmacological predictions, contribute to our understanding of their potential therapeutic utility, although further research may be warranted to address certain pharmacological aspects.

Marine-Derived Compounds as Potential Inhibitors of Hsp90 for Anticancer and Antimicrobial Drug Development: A Comprehensive In Silico Study.

Marine compounds constitute a diverse and invaluable resource for the discovery of bioactive substances with promising applications in the pharmaceutical development of anti-inflammatory and antibacterial agents. In this study, a comprehensive methodology was employed, encompassing pharmacophore modeling, virtual screening, in silico ADMET assessment (encompassing aspects of absorption, distribution, metabolism, excretion, and toxicity), and molecular dynamics simulations. These methods were applied to identify new inhibitors targeting the Hsp90 protein (heat shock protein 90), commencing with a diverse assembly of compounds sourced from marine origins. During the virtual screening phase, an extensive exploration was conducted on a dataset comprising 31,488 compounds sourced from the CMNPD database, characterized by a wide array of molecular structures. The principal objective was the development of structure-based pharmacophore models, a valuable approach when the pool of known ligands is limited. The pharmacophore model DDRRR was successfully constructed within the active sites of the Hsp90 crystal structure. Subsequent docking studies led to the identification of six compounds (CMNPD 22591, 9335, 10015, 360799, 15115, and 20988) demonstrating substantial binding affinities, each with values below -8.3 kcal/mol. In the realm of in silico ADMET predictions, five of these compounds exhibited favorable pharmacokinetic properties. Furthermore, molecular dynamics simulations and total binding energy calculations using MM-PBSA indicated that these marine-derived compounds formed exceptionally stable complexes with the Hsp90 receptor over a 100-nanosecond simulation period. These findings underscore the considerable potential of these novel marine compounds as promising candidates for anticancer and antimicrobial drug development.

Spices as Sustainable Food Preservatives: A Comprehensive Review of Their Antimicrobial Potential.

Throughout history, spices have been employed for their pharmaceutical attributes and as a culinary enhancement. The food industry widely employs artificial preservatives to retard the deterioration induced by microbial proliferation, enzymatic processes, and oxidative reactions. Nevertheless, the utilization of these synthetic preservatives in food products has given rise to significant apprehension among consumers, primarily stemming from the potential health risks that they pose. These risks encompass a spectrum of adverse effects, including but not limited to gastrointestinal disorders, the disruption of gut microbiota, allergic reactions, respiratory complications, and concerns regarding their carcinogenic properties. Consequently, consumers are displaying an increasing reluctance to purchase preserved food items that contain such additives. Spices, known for their antimicrobial value, are investigated for their potential as food preservatives. The review assesses 25 spice types for their inherent antimicrobial properties and their applicability in inhibiting various foodborne microorganisms and suggests further future investigations regarding their use as possible natural food preservatives that could offer safer, more sustainable methods for extending shelf life. Future research should delve deeper into the use of natural antimicrobials, such as spices, to not only replace synthetic preservatives but also optimize their application in food safety and shelf-life extension. Moreover, there is a need for continuous innovation in encapsulation technologies for antimicrobial agents. Developing cost-effective and efficient methods, along with scaling up production processes, will be crucial to competing with traditional antimicrobial options in terms of both efficacy and affordability.

Combination of sweet orange, lentisk and lemon eucalyptus essential oils: Optimization of a new complete antimicrobial formulation using a mixture design methodology.

Sweet orange (Citrus × sinensis (L.) Osbeck), lentisk (Pistacia lentiscus L.) and lemon eucalyptus (Eucalyptus citriodora Hook) are medicinal plants known by its culinary virtues. Their volatile oils have demonstrated promising antimicrobial activity against a panel of microbial strains, including those implicated in food deterioration. In this exploratory investigation, we aimed to determine the antimicrobial formulation of sweet orange, lentisk and lemon eucalyptus essential oils (EOs) using the simplex-centroid mixture design approach coupled with a broth microdilution method. EOs were first extracted by hydrodistillation, and then their phytochemical profile was characterized using Gas chromatography-mass spectrometry (GC-MS). GC-MS analysis identified d-limonene (14.27%), careen-3 (14.11%), ß-myrcene (12.53%) as main components of lentisk EOs, while lemon eucalyptus was dominated by citronellal (39.40%), ß-citronellol (16.39%) and 1,8-cineole (9.22%). For sweet orange EOs, d-limonene (87.22%) was the principal compound. The three EOs exhibited promising antimicrobial potential against various microorganisms. Lemon eucalyptus and sweet orange EO showed high activity against most tested microorganisms, while lentisk EO exerted important effect against some microbes but only moderate activity against others. The optimization formulations of antimicrobial potential showed interesting synergistic effects between three EOs. The best combinations predicted on C. albicans, S. aureus, E. coli, S. enterica and B. cereus correspond to 44%/55%/0%, 54%/16%/28%, 43%/22%/33%, 45%/17%/36% and 36%/30%/32% of Citrus sinensis, Pistacia lentiscus and Eucalyptus citriodora EOs, respectively. These findings suggest that the combination of EOs could be used as natural food preservatives and antimicrobial agents. However, further studies are needed to determine the mechanisms of action and efficacy of these EOs against different microorganisms.

Unveiling the volatile compounds and antibacterial mechanisms of action of Cupressus sempervirens L., against Bacillus subtilis and Pseudomonas aeruginosa.

Cupressus sempervirens is a known traditional plant used to manage various ailments, including cancer, inflammatory and infectious diseases. In this investigation, we aimed to explore the chemical profile of Cupressus sempervirens essential oil (CSEO) as well as their antibacterial mode of action. The volatile components were characterized using gas chromatography coupled to a mass spectrometer (GC-MS). The results revealed remarkable antibacterial properties of EO derived from C. sempervirens. GC-MS analysis indicated that C. sempervirens EO characterized by δ-3-carene (47.72%), D-limonene (5.44%), ß-pinene (4.36%), ß-myrcene (4.02%). The oil exhibited significant inhibitory effects against a range of bacteria, including Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 13048, Bacillus cereus (Clinical isolate), Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922. These inhibitory effects surpassed those of conventional antibiotics. Furthermore, the EO demonstrated low minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs), indicating its bactericidal nature (MBC/MIC < 4.0). Time-kill kinetics analysis showed that CSEO was particularly effective at 2 × MIC doses, rapidly reduced viable count of B. subtilis and P. aeruginosa within 8 h. This suggests that the oil acts quickly and efficiently. The cell membrane permeability test further demonstrated the impact of CSEO on the relative conductivity of B. subtilis and P. aeruginosa, both at 2 × MIC concentrations. These observations suggest that EO disrupts the bacterial membrane, thereby influencing their growth and viability. Additionally, the cell membrane integrity test indicated that the addition of CSEO to bacterial cultures resulted in the significant release of proteins from the bacterial cells. This suggests that EO affects the structural integrity of the bacterial cells. Furthermore, the anti-biofilm assay confirmed the efficacy of CSEO as a potent anti-biofilm agent. It demonstrated the oil's ability to inhibit quorum sensing, a crucial mechanism for biofilm formation, and its competitive performance compared to the tested antibiotics.

Back to Nature: Medicinal Plants as Promising Sources for Antibacterial Drugs in the Post-Antibiotic Era.

Undoubtedly, the advent of antibiotics in the 19th century had a substantial impact, increasing human life expectancy. However, a multitude of scientific investigations now indicate that we are currently experiencing a phase known as the post-antibiotic era. There is a genuine concern that we might regress to a time before antibiotics and confront widespread outbreaks of severe epidemic diseases, particularly those caused by bacterial infections. These investigations have demonstrated that epidemics thrive under environmental stressors such as climate change, the depletion of natural resources, and detrimental human activities such as wars, conflicts, antibiotic overuse, and pollution. Moreover, bacteria possess a remarkable ability to adapt and mutate. Unfortunately, the current development of antibiotics is insufficient, and the future appears grim unless we abandon our current approach of generating synthetic antibiotics that rapidly lose their effectiveness against multidrug-resistant bacteria. Despite their vital role in modern medicine, medicinal plants have served as the primary source of curative drugs since ancient times. Numerous scientific reports published over the past three decades suggest that medicinal plants could serve as a promising alternative to ineffective antibiotics in combating infectious diseases. Over the past few years, phenolic compounds, alkaloids, saponins, and terpenoids have exhibited noteworthy antibacterial potential, primarily through membrane-disruption mechanisms, protein binding, interference with intermediary metabolism, anti-quorum sensing, and anti-biofilm activity. However, to optimize their utilization as effective antibacterial drugs, further advancements in omics technologies and network pharmacology will be required in order to identify optimal combinations among these compounds or in conjunction with antibiotics.

Pharmacoinformatics and Breed-Based De Novo Hybridization Studies to Develop New Neuraminidase Inhibitors as Potential Anti-Influenza Agents.

Influenza represents a profoundly transmissible viral ailment primarily afflicting the respiratory system. Neuraminidase inhibitors constitute a class of antiviral therapeutics employed in the management of influenza. These inhibitors impede the liberation of the viral neuraminidase protein, thereby impeding viral dissemination from the infected cell to host cells. As such, neuraminidase has emerged as a pivotal target for mitigating influenza and its associated complications. Here, we apply a de novo hybridization approach based on a breed-centric methodology to elucidate novel neuraminidase inhibitors. The breed technique amalgamates established ligand frameworks with the shared target, neuraminidase, resulting in innovative inhibitor constructs. Molecular docking analysis revealed that the seven synthesized breed molecules (designated Breeds 1-7) formed more robust complexes with the neuraminidase receptor than conventional clinical neuraminidase inhibitors such as zanamivir, oseltamivir, and peramivir. Pharmacokinetic evaluations of the seven breed molecules (Breeds 1-7) demonstrated favorable bioavailability and optimal permeability, all falling within the specified parameters for human application. Molecular dynamics simulations spanning 100 nanoseconds corroborated the stability of these breed molecules within the active site of neuraminidase, shedding light on their structural dynamics. Binding energy assessments, which were conducted through MM-PBSA analysis, substantiated the enduring complexes formed by the seven types of molecules and the neuraminidase receptor. Last, the investigation employed a reaction-based enumeration technique to ascertain the synthetic pathways for the synthesis of the seven breed molecules.

Antioxidant, Volatile Compounds; Antimicrobial, Anti-Inflammatory, and Dermatoprotective Properties of Cedrus atlantica (Endl.) Manetti Ex Carriere Essential Oil: In Vitro and In Silico Investigations.

Cedrus atlantica (Endl.) Manetti ex Carriere is an endemic tree possessing valuable health benefits which has been widely used since time immemorial in international traditional pharmacopoeia. The aim of this exploratory investigation is to determine the volatile compounds of C. atlantica essential oils (CAEOs) and to examine their in vitro antimicrobial, antioxidant, anti-inflammatory, and dermatoprotective properties. In silico simulations, including molecular docking and pharmacokinetics absorption, distribution, metabolism, excretion, and toxicity (ADMET), and drug-likeness prediction were used to reveal the processes underlying in vitro biological properties. Gas chromatography-mass spectrophotometry (GC-MS) was used for the chemical screening of CAEO. The antioxidant activity of CAEO was investigated using four in vitro complementary techniques, including ABTS and DPPH radicals scavenging activity, ferric reductive power, and inhibition of lipid peroxidation (ß-carotene test). Lipoxygenase (5-LOX) inhibition and tyrosinase inhibitory assays were used for testing the anti-inflammatory and dermatoprotective properties. GC-MS analysis indicated that the main components of CAEO are ß-himachalene (28.99%), α-himachalene (14.43%), and longifolene (12.2%). An in vitro antimicrobial activity of CAEO was examined against eleven strains of Gram-positive bacteria (three strains), Gram-negative bacteria (four strains), and fungi (four strains). The results demonstrated high antibacterial and antifungal activity against ten of them (>15 mm zone of inhibition) using the disc-diffusion assay. The microdilution test showed that the lowest values of MIC and MBC were recorded with the Gram-positive bacteria in particular, which ranged from 0.0625 to 0.25 % v/v for MIC and from 0.5 to 0.125 % v/v for MBC. The MIC and MFC of the fungal strains ranged from 0.5 to 4.0% (MIC) and 0.5 to 8.0% v/v (MFC). According to the MBC/MIC and MFC/MIC ratios, CAEO has bactericidal and fungicidal activity. The results of the in vitro antioxidant assays revealed that CAEO possesses remarkable antioxidant activity. The inhibitory effects on 5-LOX and tyrosinase enzymes was also significant (p < 0.05). ADMET investigation suggests that the main compounds of CAEO possess favorable pharmacokinetic properties. These findings provide scientific validation of the traditional uses of this plant and suggest its potential application as natural drugs.

Galactoside-Based Molecule Enhanced Antimicrobial Activity through Acyl Moiety Incorporation: Synthesis and In Silico Exploration for Therapeutic Target.

In this study, a series of galactoside-based molecules, compounds of methyl ß-d-galactopyranoside (MDGP, 1), were selectively acylated using 2-bromobenzoyl chloride to obtain 6-O-(2-bromobenzoyl) substitution products, which were then transformed into 2,3,4-tri-O-6-(2-bromobenzoyl) compounds (2-7) with various nontraditional acyl substituents. The chemical structures of the synthesized analogs were characterized by spectroscopic methods and physicochemical and elemental data analyses. The antimicrobial activities of the compounds against five human pathogenic bacteria and two phyto-fungi were evaluated in vitro and it was found that the acyl moiety-induced synthesized analogs exhibited varying levels of antibacterial activity against different bacteria, with compounds 3 and 6 exhibiting broad-spectrum activity and compounds 2 and 5 exhibiting activity against specific bacteria. Compounds 3 and 6 were tested for MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) based on their activity. The synthesized analogs were also found to have potential as a source of new antibacterial agents, particularly against gram-positive bacteria. The antifungal results suggested that the synthesized analogs could be a potential source of novel antifungal agents. Moreover, cytotoxicity testing revealed that the compounds are less toxic. A structure-activity relationship (SAR) investigation revealed that the lauroyl chain [CH3(CH2)10CO-] and the halo-aromatic chain [3(/4)-Cl.C6H4CO-] in combination with sugar, had the most potent activity against bacterial and fungal pathogens. Density functional theory (DFT)-calculated thermodynamic and physicochemical parameters, and molecular docking, showed that the synthesized molecule may block dengue virus 1 NS2B/NS3 protease (3L6P). A 150 ns molecular dynamic simulation indicated stable conformation and binding patterns in a stimulating environment. In silico ADMET calculations suggested that the designed (MDGP, 1) had good drug-likeness values. In summary, the newly synthesized MDGP analogs exhibit potential antiviral activity and could serve as a therapeutic target for dengue virus 1 NS2B/NS3 protease.

Phytochemical analysis and evaluation of antimicrobial, antioxidant, and antidiabetic activities of essential oils from Moroccan medicinal plants: Mentha suaveolens, Lavandula stoechas, and Ammi visnaga.

Mentha suaveolens, Lavandula stoechas, and Ammi visnaga are widely used in Moroccan folk medicine against several pathological disorders, including diabetes and infectious diseases. This work was designed to determine the chemical profile of M. suaveolens (MSEO), L. stoechas (LSEO), and A. visnaga (AVEO) essential oils and assess their antimicrobial, antioxidant, and antidiabetic effects. The volatile components of LSEO, AVEO, and MSEO were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The in vitro antidiabetic activity was assessed using α-amylase and α-glucosidase enzymes, while DPPH, FRAP, and ß-carotene/linoleic acid methods were used to determine the antioxidant capacity. The antimicrobial activities were investigated using disc diffusion and broth-microdilution assays. GC-MS investigation revealed that the main components were fenchone (29.77 %) and camphor (24.9 %) for LSEO, and linalool (38.29 %) for AVEO, while MSEO was mainly represented by piperitenone oxide (74.55 %). The results of the antimicrobial evaluation showed that all examined essential oils (EOs) had noticeable antimicrobial activity against both bacteria and yeast, especially Micrococcus luteus and Bacillus subtilis. The MIC, MBC, and MFC values were ranged from 0.015 % to 0.5 %. The MBC/MIC and MFC/MIC ratios were less than or equal to 4.0 % (v/v), indicating their noticeable bactericidal and candidacidal efficacy. Moreover, the three EOs showed significant inhibitory effects on α-amylase and α-glucosidase (p < 0.05). It also exerted remarkable activity on FRAP, ß-carotene, and DPPH radicals. These findings demonstrated that the tested plants have promising biological activities, validating their ethnomedicinal value and providing potential applications as natural drugs.

Phytochemical, Antidiabetic, Antioxidant, Antibacterial, Acute and Sub-Chronic Toxicity of Moroccan Arbutus unedo Leaves.

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

Design, Synthesis, In Silico and POM Studies for the Identification of the Pharmacophore Sites of Benzylidene Derivatives.

Due to the uneven distribution of glycosidase enzyme expression across bacteria and fungi, glycoside derivatives of antimicrobial compounds provide prospective and promising antimicrobial materials. Therefore, herein, we report the synthesis and characterization of six novel methyl 4,6-O-benzylidene-α-d-glucopyranoside (MBG) derivatives (2-7). The structures were ascertained using spectroscopic techniques and elemental analyses. Antimicrobial tests (zone of inhibition, MIC and MBC) were carried out to determine their ability to inhibit the growth of different Gram-positive, Gram-negative bacteria and fungi. The highest antibacterial activity was recorded with compounds 4, 5, 6 and 7. The compounds with the most significant antifungal efficacy were 4, 5, 6 and 7. Based on the prediction of activity spectra for substances (PASS), compounds 4 and 7 have promising antimicrobial capacity. Molecular docking studies focused on fungal and bacterial proteins where derivatives 3 and 6 exhibited strong binding affinities. The molecular dynamics study revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and endoglucanase from Aspergillus niger remained stable, both over time and in physiological conditions. Structure-activity relationships, including in vitro and in silico results, revealed that the acyl chains [lauroyl-(CH3(CH2)10CO-), cinnamoyl-(C6H5CH=CHCO-)], in combination with sugar, were found to have the most potential against human and fungal pathogens. Synthetic, antimicrobial and pharmacokinetic studies revealed that MBG derivatives have good potential for antimicrobial activity, developing a therapeutic target for bacteria and fungi. Furthermore, the Petra/Osiris/Molinspiration (POM) study clearly indicated the presence of an important (O1δ-----O2δ-) antifungal pharmacophore site. This site can also be explored as a potential antiviral moiety.

Unveiling Chemical, Antioxidant and Antibacterial Properties of Fagonia indica Grown in the Hail Mountains, Saudi Arabia.

The Aja and Salma mountains in the Hail region are home to a variety of indigenous wild plants, some of which are used in Bedouin folk medicine to treat various ailments. The purpose of the current study was to unveil the chemical, antioxidant and antibacterial properties of Fagonia indica (Showeka) grown widely in these mountains, as data on the biological activities of this plant in this remote area are scarce. XRF spectrometry indicated the presence of some essential elements, which were in the order of Ca > S > K > AL > CL > Si > P > Fe > Mg > Na > Ti > Sr > Zn > Mn. Qualitative chemical screening revealed the presence of saponins, terpenes, flavonoids, tannins, phenols and cardiac glycosides in the methanolic extract (80% v/v). GC-MS showed the presence of 2-chloropropanoic acid 18.5%, tetrahydro-2-methylfuran 20.1%, tridecanoic acid 12-methyl-, methyl ester 2.2%, hexadecanoic acid, methyl ester 8.6%, methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate 13.4%, methyl linoleate 7.0%, petroselinic acid methyl ester 15%, erucylamide 6.7% and diosgenin 8.5%. Total phenols, total tannins, flavonoids, DPPH, reducing power, -carotene and ABTS IC50 (mg/mL) scavenging activity were used to measure the antioxidant capabilities of Fagonia indica, which exhibited prominent antioxidant properties at low concentrations when compared to ascorbic acid, butylate hydroxytoluene and beta-carotene. The antibacterial investigation revealed significant inhibitory effects against Bacillus subtilis MTCC121 and Pseudomona aeruginosa MTCC 741 with inhibition zones of 15.00 ± 1.5 and 12.0 ± 1.0 mm, respectively. The MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) ranged between 125 to 500 µg/mL. The MBC/MIC ratio indicated possible bactericidal efficacy against Bacillus subtilis and bacteriostatic activity against Pseudomona aeruginosa. The study also showed that this plant has anti-biofilm formation activity.

Inhibitory Activity of Saussurea costus Extract against Bacteria, Candida, Herpes, and SARS-CoV-2.

Medicinal herbs have long been utilized to treat various diseases or to relieve the symptoms of some ailments for extended periods. The present investigation demonstrates the phytochemical profile, molecular docking, anti-Candida activity, and anti-viral activity of the Saussurea costus acetic acid extract. GC-MS analysis of the extract revealed the presence of 69 chemical compounds. The chemical compounds were alkaloids (4%), terpenoids (79%), phenolic compounds (4%), hydrocarbons (7%), and sterols (6%). Molecular docking was used to study the inhibitory activity of 69 identified compounds against SARS-CoV-2. In total, 12 out of 69 compounds were found to have active properties exhibiting SARS-CoV-2 inhibition. The binding scores of these molecules were significantly low, ranging from -7.8 to -5.6 kcal/mol. The interaction of oxatricyclo [20.8.0.0(7,16)] triaconta-1(22),7(16),9,13,23,29-hexaene with the active site is more efficient. Furthermore, the extract exhibited significant antimicrobial activity (in vitro) against Candida albicans, which was the most susceptible microorganism, followed by Bacillus cereus, Salmonella enterica, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, respectively. On the other hand, its antiviral activity was evaluated against HSV-1 and SARS-CoV-2, and the results showed a significant positive influence against HSV-1 (EC50 = 82.6 g/mL; CC50 = 162.9 g/mL; selectivity index = 1.9). In spite of this, no impact could be observed in terms of inhibiting the entry of SARS-CoV-2 in vitro.

Biological and Pharmacological Properties of Myrtenol: A Review.

Myrtenol (C10H16O) is a volatile compound belonging to the terpenoid family of monocyclic monoterpenes. It is one of the essential oils constituents of several aromatic plants, including the genera Myrtus, Tanacetum, Artemisia, Hyssopus, and Rhodiola. The oxidation of α-pinene can produce it. Several reports demonstrated the pharmacological properties of myrtenol, including its antioxidant, antibacterial, antifungal, antidiabetic, anxiolytic, and gastroprotective activities. In this review, we discussed and highlighted in depth the pharmacological activities, cellular and molecular, providing insight into the mechanisms of myrtenol. In light of this finding, the interesting biological activities and abundance of myrtenol in nature suggests its potential applications in medicinal settings in the fight against various diseases.

Lipid nanoparticles technology in vaccines: Shaping the future of prophylactic medicine.

Throughout decades, the intrinsic power of the immune system to fight pathogens has inspired researchers to develop techniques that enable the prevention or treatment of infections via boosting the immune response against the target pathogens, which has led to the evolution of vaccines. The recruitment of Lipid nanoparticles (LNPs) as either vaccine delivery platforms or immunogenic modalities has witnessed a breakthrough recently, which has been crowned with the development of effective LNPs-based vaccines against COVID-19. In the current article, we discuss some principles of such a technology, with a special focus on the technical aspects from a translational perspective. Representative examples of LNPs-based vaccines against cancer, COVID-19, as well as other infectious diseases, autoimmune diseases, and allergies are highlighted, considering the challenges and promises. Lastly, the key features that can improve the clinical translation of this area of endeavor are inspired.

Impact of COVID-19 infection on the dialysis population prospective, observational, nationwide study.

INTRODUCTION: Hemodialysis (HD) patients are at increased risk of severe COVID-19 infection but infection rates vary. Our objectives are to describe COVID-19 positive HD patients' characteristics, infection rates, and factors associated with mortality in HD COVID-19 cases in Kuwait. METHODS: Data on demographics, comorbidities, and treatments received, as well as mortality for HD patients admitted to hospitals for COVID-19, from 1/March to 31/July 2020, prospectively collected and analyzed. RESULTS: A total of 141 infected HD patients were admitted (Mean age 58 ± 16.1; Males 56%), representing 7% of the total HD population and 0.2% of all COVID-19 cases during the study period. Of those 141 infected HD patients, 27 (19%) died, and this represents 6% of total COVID-19-related mortality and 27% of the total HD mortality. In contrast, total covid-19-related mortality of all positive cases was only 0.7%, and total HD mortality during the study period was only 5%. COVID-19-positive HD patients who died were older and 59% were males. However, the differences were not statistically significant. Of the 61 infected HD patients who needed to be switched to continuous kidney replacement therapy (CKRT), 34% died, and of the 29 infected HD patients who needed admission to intensive care, 65% died. CONCLUSION: HD population represents a small fraction of the total population; however, positive HD COVID-19 cases represent a sizable proportion of COVID-19 cases and a significant percentage of total COVID-19-related mortality, and total HD mortality.

In Vitro Influence of ZnO, CrZnO, RuZnO, and BaZnO Nanomaterials on Bacterial Growth.

In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria's growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings.