Two novel synthetic xanthenodiones as antimicrobial, anti-adhesive and antibiofilm compounds against methicillin resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is widely recognized as a causative agent for various infections acquired in healthcare settings as well as in the community. Given the limited availability of effective antimicrobial agents to combat MRSA infections, there is an increasing need to explore alternative therapeutic strategies. This study aimed to assess the antimicrobial, anti-adhesive, anti-biofilm properties, and toxicity of 175 newly synthesized compounds, belonging to seven different classes, against MRSA. Initially, the compounds underwent screening for antimicrobial activity using the agar diffusion method. Subsequently, active compounds underwent further evaluation to determine their minimum inhibitory concentrations through microdilution. Anti-biofilm and anti-adhesive properties were assessed using the crystal violet method, while toxicity was tested using the alternative infection model Galleria mellonella. Among the tested compounds, two xanthenodiones exhibited the most promising activities, displaying bactericidal effects along with anti-adhesive and anti-biofilm properties. Moreover, the observed non-toxicity in G. mellonella larvae suggests that these compounds hold significant potential as alternative therapeutic options to address the escalating challenge of MRSA resistance in both hospital and community settings.

Formulations of essential oils obtained from plants traditionally used as condiments or traditional medicine active against Staphylococcus aureus isolated from dairy cows with mastitis.

The prophylactic and therapeutic overuse of antimicrobials on the farm has contributed to the emergence of hard-to-fight bacterial strains causing bovine mastitis. Aiming at alternative therapies, this study evaluated the antimicrobial activity of 20 essential oils against clinical Staphylococcus aureus strains. Of them, five with strong activities were selected and evaluated for their minimum inhibitory concentrations (MIC) in culture medium and milk, cytotoxicity against bovine mammary cells (MAC-T), antiadhesive properties, and interactions among themselves and with cefoperazone. The oils remained active on milk, were not cytotoxic, and some concentrations stimulated MAC-T cells growth, suggesting healing potential. Subinhibitory concentrations of Coriandrum sativum, Origanum vulgare, Syzygium aromaticum, and Thymus vulgaris reduced biofilm formation by at least 80%. Several oil and cefoperazone combinations displayed additive interaction, with O. vulgare and C. sativum showing the most promising results. We developed formulations for being used as prophylactic postdipping solutions in the field, containing different concentrations (1% or 3%) of the active oils, alone or in combination, with 3% glycerin, 1% Tween 80, and water. The formulations showed strong antimicrobial activity in milk and enhanced antiadhesive properties, specially when two oils were combined in the formula, indicating promising biotechnological and therapeutical applications.

Salvinia auriculata: chemical profile and biological activity against Staphylococcus aureus isolated from bovine mastitis.

The aquatic plant Salvinia auriculata has been shown to possess promising properties for the treatment of Staphylococcus aureus bovine mastitis. The disease affects cattle health and compromises dairy cattle productivity, resulting in reduced milk production and higher mortality rates. The aim of this study was to evaluate the antimicrobial activity, antibiofilm activity, and toxicity of S. auriculata root extracts using bovine mammary epithelial cells (MAC-T); determine the chemical composition of the most active extract; and develop an S. auriculata antiseptic solution for pre- and post-milking teat disinfection. Plants were collected during the four seasons of the year. The most active hexane extract was subjected to bioguided fractionation, which resulted in the isolation of six known compounds, stigmast-22-ene-3,6-dione, stigmasterol, friedelinol, ß-sitosterol, octadecyl alcohol, and octadecanoic acid. The antimicrobial and antibiofilm activities of the most active extract and isolated compounds were determined against nine S. aureus strains isolated from cows with mastitis. The efficacy of the S. auriculata teat dip formulation was tested using an excised teat model (ex vivo), and promising results were obtained. The S. auriculata extract formulation proved to be as effective as commercial antimicrobials in reducing log counts in excised teats.

Stereoselective synthesis of (-)-cytoxazone and its unnatural congener (+)-5-epi-cytoxazone.

An interesting protocol for stereoselective synthesis of (-)-cytoxazone and its unnatural stereoisomer (+)-5-epi-cytoxazone from d-4-hydroxyphenylglycine in overall yields of 10% and 16%, respectively, is described. The stereoselective addition of cyanide to an N-Boc protected aminoaldehyde (tert-butyl ((R)-1-(4-methoxyphenyl)-2-oxoethyl)carbamate) (5) constitutes the key step in this approach, producing a mixture of cyanohydrins 6a and b (1,2-anti and 1,2-syn tert-butyl (2-cyano-2-hydroxy-1-(4-methoxyphenyl)ethyl)carbamate) in 89% yield, with reasonable stereoselectivity (1.0:1.8) in favor of the anti-Felkin product (1,2-syn). A one-pot sequence of three successive steps from this mixture produced the oxazolidinone isomers 9a and b ((4R,5R)- and (4R,5S)-4-(4-methoxyphenyl)-2-oxooxazolidine-5-carboxylate). Chromatographic column separation and reduction of the ester function of both precursors led to (-)-cytoxazone and (+)-5-epi-cytoxazone.

Antioxidant study indicative of antibacterial and antimutagenic activities of an ellagitannin-rich aqueous extract from the leaves of Miconia latecrenata.

Ethnopharmacological relevance; Several plant species of Miconia genus are commonly used in Brazilian folk medicine as anti-inflammatory agents and for the treatment of infectious diseases. Infusions and extracts of Miconia species are also reported as analgesic, antimicrobial, antimalarial, antioxidant, anti-inflammatory, antinociceptive, antimutagenic, and antitumoral. Aim of the study; To determine the phytochemical composition of an aqueous extract of Miconia latecrenata leaves and to evaluate its antioxidant, antibacterial, antimutagenic and antigenotoxic activities. Materials and Methods; The following methods were used for the different effects: I) antioxidant - ß-carotene/linoleic acid, lipid peroxidation, and DPPH• radical scavenging; II) antibacterial - agar well diffusion and MIC methods); III) antimutagenic assays - Ames Test; and IV) antigenotoxic - Plasmid cleavage test. The phytochemical analysis and phenolic quantification were carried out by UPLC-DAD-ESI-MS/MS and colorimetry, respectively. In addition, statistical correlation analysis was performed aiming to evaluate the Pearson correlation between phenolic compounds and biological assays. Results; A high content of tannins was observed and the ellagitannin isomers of 1,2,3,5-tris-galloyl-4,6-HHDP-glucose were identified as the main constituents of the leaves aqueous extract. High antioxidant effect, in different tests, high antibacterial activity to gram-positive and negative strains, as well as high antimutagenic activity were observed. Statistical analysis showed a high Pearson correlation for the tannin content in relation to the results of the antioxidant and antibacterial tests. In general, the antioxidant action of the aqueous extract showed low correlation with the antimutagenic activity. Conclusions; The present results confirmed the expectations regarding the pharmacological profile of M. latecrenata supporting its therapeutic potential in relation to ROS/RNS related disorders. Furthermore, the phenolic compounds of M. latecrenata can act, in turn, minimizing or inhibiting the biological macromolecules damage, especially DNA.

Evaluation of the antiviral activities of Bacharis dracunculifolia and quercetin on Equid herpesvirus 1 in a murine model.

Equid herpesvirus 1 (EHV-1) is a pathogen of high economic importance in equine breeding operations around the world. EHV-1 infection causes respiratory, neurologic and reproductive disease. The absence of an efficient therapy has caught the attention of the scientific community and the therapeutic activities of natural products with its antivirals effects might be effective for the disease's treatment. Herein it was evaluated the prophylactic and therapeutic potential of quercetin and ethanolic extracts of Bacharis dracunculifolia formulations compared to Penciclovir® in an in vivo EHV-1 infection model. Six to seven-week-old female C57BL/6 mice were randomly organized into fifteen groups with six animals each. Ex-1 represents the treatment post-challenge groups to assess morbidity, mortality and weight variation. Ex-2 represents the animals that received treatment for 5 days post-challenge for lesion evaluation. In Ex-3 animals were treated prior to viral challenge to assess morbidity, mortality and weight variation. All mice in the treatment groups were challenged by intranasal inoculation of 3.0 × 105 TCID50 EHV-1. The quercetin and B. dracunculifolia treatment decreased morbimortality in post-challenge treatment (Ex-1) and EHV-1 related lesions (Ex-2). Treatment prior to viral challenge (Ex-3) did not show any significant results. Based on the results of the present study, both tested formulations are promising antiviral agents for the treatment of EHV-1 infection.

Phytochemical characterization and antioxidant, antibacterial and antimutagenic activities of aqueous extract from leaves of Alchornea glandulosa.

Plant extracts exist as a complex matrix which serves as a source of numerous bioactive metabolites. The ultra performance liquid chromatography with diode-array detection-coupled electrospray ionization-mass spectrometry/mass spectrometry technique was used to characterize the aqueous extract from leaves of Alchornea glandulosa (EAG), a species popularly used to treat gastrointestinal problems as an antiulcer agent. Quantification of phenolic derivatives was determined using Folin-Ciocalteu and aluminum trichloride (AlCl3) methods. In addition, antioxidant (2,2-diphenyl-1-picrylhydrazyl [DPPH•] radical scavenging, ß-carotene-linoleic acid, and lipid peroxidation), antibacterial (agar well diffusion method and minimum inhibitory concentration), antimutagenic (Ames test), and antigenotoxic (plasmid cleavage) assays were also performed on this plant extract. The ellagitannin tris-galloyl-hexahydroxydiphenic acid-glucose was identified as the predominant compound along with tannins as majority metabolites. EAG showed high antioxidant activity accompanied by moderate antibacterial activity against Staphylococcus aureus. The highest antimutagenic activity was observed for TA97 strain without metabolic activation (S9) and with metabolic activation, TA100 and TA102 were completely inhibited. In addition, EAG exhibited potential signs of antigenotoxic action. The high antioxidant and antimutagenic activity observed for EAG suggests important therapeutic uses that still need to be verified in future studies.

Identification of phenolic compounds and biologically related activities from Ocotea odorifera aqueous extract leaves.

Ocotea odorifera (Vell.) Rohwer is popularly used as food and flavoring. The aim of this study was to determine the chemical composition of the aqueous extract from O. odorifera leaves and evaluate the correlation of their phytochemical composition and biological activities. The antioxidant effect was determined by DPPH radical scavenging, ß-carotene-linoleic acid and lipid peroxidation assays; the antibacterial activity was evaluated by the hole plate and MIC techniques and the antimutagenic activity was evaluated by the Ames test. Identification of phytochemicals was performed by LC-ESI/MS and the correlation between the phytochemical composition of the extract and the evaluated activities. The results allowed the identification of 13 phenolic compounds in the extract that exhibited high antioxidant activity and moderate antibacterial and antimutagenic action. Statistical analyses showed correlation of the total phenolic content with biologically related activities. The phytochemical analyses, together with the biological results, support the popular use of O. odorifera.

Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences.

Osteoporosis is a public health concern associated with an increased risk of bone fractures and vascular calcification. Vitamin K presents unique benefits on these issues, although understudied. The two main forms of vitamin K are phylloquinone (vitamin K1) and menaquinone (vitamin K2). In this study, it was especially investigated the action of vitamin K2 in bones and vessels. Vitamin K2 has shown to stimulate bone formation by promoting osteoblast differentiation and carboxylation of osteocalcin, and increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15, and stanniocalcin 2 levels. Furthermore, vitamin K2 reduces the pro-apoptotic proteins Fas and Bax in osteoblasts, and decreases osteoclast differentiation by increasing osteoprotegerin and reducing the receptor activator of nuclear factor kappa-B ligand. In blood vessels, vitamin K2 reduces the formation of hydroxyapatite, through the carboxylation of matrix Gla protein and Gla rich protein, inhibits the apoptosis of vascular smooth muscle cells, by increasing growth arrest-specific gene 6, and reduces the transdifferentiation of vascular smooth muscle cells to osteoblasts. The commonly used dosage of vitamin K2 in human studies is 45 mg/day and its application can be an interesting strategy in benefitting bone and vascular health, especially to osteoporotic post-menopausal women.

Chemical Constituents and an Alternative Medicinal Veterinary Herbal Soap Made from Senna macranthera.

Upon undergoing biomonitoring, the most active dichloromethane extract retrieved from Senna macranthera roots led to the isolation of three main compounds: emodine, physione, and chrysophanol. In this sequence, these compounds revealed a potential antibacterial activity against Staphylococcus aureus strains isolated from animals with mastitis infections with minimum inhibitory concentration (MIC) values of 20, 90, and 90 µg mL(-1), respectively. Therefore, an herbal soap was also produced from this same active extract. This soap was tested in vitro using gloves contaminated by animals with bovine mastitis that had been discarded after use by milkers and showed similar results to previously tested compounds. These results indicate the potential of this plant as an alternative veterinary medicine for the production of antibacterial soaps that aimed at controlling bovine mastitis infections in small Brazilian farms.

Antibacterial Chemical Constituent and Antiseptic Herbal Soap from Salvinia auriculata Aubl.

The bioassay-guided isolation of the active extract of Salvinia auriculata Aubl. led to the separation of three main compounds, characterized as stigmasterone, stigmasterol, and friedelinol. The pure form of diketosteroid presented a potential antibacterial activity with a minimum inhibitory concentration (MIC) value of 0.01 mg mL(-1) against Staphylococcus aureus isolated from animals with mastitis infections. The active extract also showed a similar result to that previously obtained with pure diketosteroid when tested with the same isolates. The present study's results demonstrate the potential of this plant as an excipient for the production of antibacterial soaps aimed at controlling bovine mastitis infections, especially on small farms.