Antibacterial Activity of Thymus vulgaris L. Essential Oil Vapours and Their GC/MS Analysis Using Solid-Phase Microextraction and Syringe Headspace Sampling Techniques

While the inhalation of Thymus vulgaris L. essential oil (EO) is commonly approved for the treatment of mild respiratory infections, there is still a lack of data regarding the antimicrobial activity and chemical composition of its vapours. The antibacterial activity of the three T. vulgaris EOs against respiratory pathogens, including Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pyogenes, was assessed in both liquid and vapour phases using the broth microdilution volatilisation (BMV) method. With the aim of optimising a protocol for the characterisation of EO vapours, their chemical profiles were determined using two headspace sampling techniques coupled with GC/MS: solid-phase microextraction (HS-SPME) and syringe headspace sampling technique (HS-GTS). All EO sample vapours exhibited antibacterial activity with minimum inhibitory concentrations (MIC) ranging from 512 to 1024 μg/mL. According to the sampling technique used, results showed a different distribution of volatile compounds. Notably, thymol was found in lower amounts in the headspace—peak percentage areas below 5.27% (HS-SPME) and 0.60% (HS-GTS)—than in EOs (max. 48.65%), suggesting that its antimicrobial effect is higher in vapour. Furthermore, both headspace sampling techniques were proved to be complementary for the analysis of EO vapours, whereas HS-SPME yielded more accurate qualitative results and HS-GTS proved a better technique for quantitative analysis.     

Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.     

Variation in the Antibacterial and Antioxidant Activities of Essential Oils of Five New Eucalyptus urophylla S.T. Blake Clones in Thailand

Eucalyptus oils are widely used for a variety of purposes. This study investigates the terpenoid compositions and antibacterial and antioxidant activities of eucalypt leaf oils extracted from four E. urophylla clones and one E. urophylla × E. camaldulensis hybrid clone grown in Thailand. According to GC/MS analysis, the E. urophylla oils were mainly composed of 1,8-cineole, α-terpinyl acetate, β-caryophyllene, and spathulenol, while 1,8-cineole, α-terpinyl acetate, p-cymene, and γ-terpinene were mostly identified in the hybrid oil. All eucalypt oils exhibited a significant bacteriostatic effect against Gram-positive bacteria, Streptococcus pyogenes, Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus. Only the hybrid oil had an effect on all Gram-negative bacteria tested, including Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa, and Enterobacter aerogenes. These oils have antibacterial properties that vary according to their terpenoid content. Only the hybrid oil had a potent antioxidant effect, with an IC₅₀ value of 4.21 ± 0.35 mg/mL for free radical (DPPH) scavenging. This oil’s antioxidant effect may be a result of the phenolic terpenoids, thymol and carvacrol. As a result, these oils may be a novel source of antibacterial and antioxidant agents. Additionally, the antibacterial and antioxidant capabilities of the E. urophylla × E. camaldulensis hybrid essential oil are reported for the first time.     

Synthesis of Cu-TiNT,characterization, and antibacterial properties evaluation

Copper ion–exchanged titanate nanotubes (Cu-TiNTs) had been prepared from a simple ion-exchange reaction between copper salt and sodium titanate nanotubes (Na-TiNT) which was synthesized by alkaline hydrothermal synthesis starting from titanium oxide of anatase phase. A thorough structural and morphological characterization of Cu-TiNT (and Na-TiNT) was done by using various material characterization techniques, such as X-ray diffraction, Raman spectroscopy, energy-dispersive X-ray spectroscopy, and transmission electron microscopy to reveal retention of tubular structure of titanate nanotubes with decoration of copper (II) oxide on the surface of the tubes as well as an exchange of Na⁺ ion by Cu²⁺ ion in the interlamellar space. The antibacterial properties of the Cu-TiNT were evaluated by broth macrodilution method using microtiter trays, with concentration ranging between 512 and 0.5 μg/mL. The Cu-TiNT demonstrated no clinically relevant antibacterial activity alone (minimum inhibitory concentration ≥ 1024 μg/mL), but when associated with gentamicin, this compound enhanced the antibiotic activity of this drugs against strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The results were very promising to the utilization of the Cu-TiNT as an adjuvant to the antibiotic therapy.     

The Chemical Compositions,and Antibacterial and Antioxidant Activities of Four Types of Citrus Essential Oils

Nanfeng mandarins (Citrus reticulata Blanco cv. Kinokuni), Xunwu mandarins (Citrus reticulata Blanco), Yangshuo kumquats (Citrus japonica Thunb) and physiologically dropped navel oranges (Citrus sinensis Osbeck cv. Newhall) were used as materials to extract peel essential oils (EOs) via hydrodistillation. The chemical composition, and antibacterial and antioxidant activities of the EOs were investigated. GC-MS analysis showed that monoterpene hydrocarbons were the major components and limonene was the predominate compound for all citrus EOs. The antibacterial testing of EOs against five different bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium) was carried out using the filter paper method and the broth microdilution method. Kumquat EO had the best inhibitory effect on B. subtilis, E. coli and S. typhimurium with MIC (minimum inhibitory concentration) values of 1.56, 1.56 and 6.25 µL/mL, respectively. All citrus EOs showed the antioxidant activity of scavenging DPPH and ABTS free radicals in a dose-dependent manner. Nanfeng mandarin EO presented the best antioxidant activity, with IC₅₀ values of 15.20 mg/mL for the DPPH assay and 0.80 mg/mL for the ABTS assay. The results also showed that the antibacterial activities of EOs might not be related to their antioxidant activities.     

Chemical Composition and Antibacterial Activity of Liquid and Volatile Phase of Essential Oils against Planktonic and Biofilm-Forming Cells of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen causing life-threatening, hard-to-heal infections associated with the presence of a biofilm. Essential oils (EOs) are promising agents to combat pseudomonal infections because of the alleged antimicrobial activity of their volatile fractions and liquid forms. Therefore, the purpose of this paper was to evaluate the antibacterial efficacy of both volatile and liquid phases of seven EOs (thyme, tea tree, basil, rosemary, eucalyptus, menthol mint, lavender) against P. aeruginosa biofilm and planktonic cells with the use of a broad spectrum of analytical in vitro methods. According to the study results, the antibacterial activity of EOs in their liquid forms varied from that of the volatile fractions. Overall, liquid and volatile forms of rosemary EO and tea tree EO displayed significant antibiofilm effectiveness. The outcomes indicate that these particular EOs possess the potential to be used in the therapy of P. aeruginosa infections.     

Green synthesis of AgNPs from aqueous extract of Oxalis corniculata and its antibiofilm and antimicrobial activity

The silver nanoparticles OC-AgNPs, synthesized from the aqueous extract of Oxalis corniculata (OC), showed antiviral activity against Herpes Simplex Virus-1 (HSV-1), and anti-biofilm, and antibacterial activities against human isolates of six multi-drug resistant (MDR) bacteria - Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, and Pseudomonas aeruginosa. The OC-AgNP was characterized by UV-Vis and FTIR spectroscopy; while its morphology and distribution were determined by transmission electron microscopy (TEM). The results revealed that the biogenic OC-AgNPs are spherical with an average diameter of 40 nm and has shown UV-Vis peak at 445 nm. The cytotoxicity and safety of OC-AgNP has been evaluated by MTT assay in Vero cells and triple-negative human breast cancer MDA-MB-468 cells. The plaque reduction assay has been used to test the antiviral activity against HSV-1F. The anti-biofilm activity was assessed by crystal violet staining, followed by light and confocal microscopy; while the antibacterial activity was determined by conventional disk-diffusion and broth-dilution methods. Moreover, the mechanism of anti-biofilm and antibacterial activity was examined by Field Emission Scanning Electron Microscopy (FESEM). The CC₅₀ (cytotoxicity) on Vero cells was 300 μg/ml; while the survival percentage of MDA-MB-468 cells was 27.12% at 20 μM and 80.97% at 100 μM of, respectively. The OC-AgNP showed moderate antiviral activity against HSV-1F at EC₅₀ of 25 μg/ml; but significantly inhibited the biofilm produced by Pseudomonus aeruginosa and Escherichia coli at 25-50 μg/ml; while at 30-50 μM we observed the dose-dependent lowering of fluorescence intensity under light and confocal microscope. Interestingly, the OC-AgNPs demonstrated significant antibacterial activity against Pseudomonas aeruginosa (20 mm), Klebsiella pneumoniae (15 mm), Escherichia coli (12 mm), Salmonella typhi (10 mm), Streptococcus pyogenes (11 mm) and Staphylococcus aureus (10 mm) with Minimum Inhibitory Concentration (MIC) of 0.65–0.90 μM (0.11- 0.153 μg), respectively. Further, the FESEM micrograph showed disruption of membrane structure with the damage of cell membrane integrity of Pseudomonus aeruginosa at its MIC.     

Polycyclic Phenol Derivatives from the Leaves of Spermacoce latifolia and Their Antibacterial and α-Glucosidase Inhibitory Activity

Three new polycyclic phenol derivatives, 2-acetyl-4-hydroxy-6H-furo [2,3-g]chromen-6-one (1), 2-(1′,2′-dihydroxypropan-2′-yl)-4-hydroxy-6H-furo [2,3-g][1]benzopyran-6-one (2) and 3,8,10-trihydroxy-4,9-dimethoxy-6H-benzo[c]chromen-6-one (8), along with seven known ones (3–7, 9 and 10) were isolated for the first time from the leaves of Spermacoce latifolia. Their structures were determined by spectroscopic analysis and comparison with literature-reported data. These compounds were tested for their in vitro antibacterial activity against four Gram-(+) bacteria: Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC), Bacillus subtilis (BS), and the Gram-(−) bacterium Escherichia coli. Compounds 1, 2, 5 and 8 showed antibacterial activity toward SA, BC and BS with MIC values ranging from 7.8 to 62.5 µg/mL, but they were inactive to MRSA. Compound 4 not only showed the best antibacterial activity against SA, BC and BS, but it further displayed significant antibacterial activity against MRSA (MIC 1.95 µg/mL) even stronger than vancomycin (MIC 3.9 µg/mL). No compounds showed inhibitory activity toward E. coli. Further bioassay indicated that compounds 1, 4, 5, 6, 8 and 9 showed in vitro α-glucosidase inhibitory activity, among which compound 9 displayed the best α-glucosidase inhibitory activity with IC₅₀ value (0.026 mM) about 15-fold stronger than the reference compound acarbose (IC₅₀ 0.408 mM). These results suggested that compounds 4, 8 and 9 were potentially highly valuable compounds worthy of consideration to be further developed as an effective anti-MRSA agent or effective α-glucosidase inhibitors, respectively. In addition, the obtained data also supported that S. latifolia was rich in structurally diverse bioactive compounds worthy of further investigation, at least in searching for potential antibiotics and α-glucosidase inhibitors.     

Chemical Composition and Biological Activities of Hedychium coccineum Buch.-Ham. ex Sm. Essential Oils from Kumaun Hills of Uttarakhand

Hedychium coccineum Buch. Ham. ex Sm. is a perennial rhizomatous herb belonging to the family Zingiberaceae. The aim of the present study was to compare the chemical composition and biological activities of H. coccineum rhizome essential oil (HCCRO) and H. coccineum aerial part essential oil (HCCAO). The plant material was subjected to hydro-distillation using Clevenger’s apparatus in order to obtain volatile oil and analyzed for its chemical constituents using GC-MS. The comparative study of the rhizome and aerial part essential oils of H. coccineum displayed that (E)-nerolidol (15.9%), bornyl acetate (13.95%), davanone B (10.9%), spathulenol (8.9%), and 1, 8-cineol (8.5%) contributed majorly to the HCCRO, while 7-hydroxyfarnesen (15.5%), α-farnesene (11.1%), α-pinene (10.9%), spathulenol (7.7%), and β-pinene (6.8%) were present as major constituents in the HCCAO. Both the essential oils were studied for their biological activities, such as nematicidal, insecticidal, herbicidal, antifungal, and antibacterial activities. The essential oils exhibited significant nematicidal activity against Meloidogyne incognita, insecticidal activity against Spodoptera litura, and moderate herbicidal activity against R. raphanistrum sub sp. sativus, and good antifungal activity against Fusarium oxysporum and Curvularialunata. Essential oils were also tested for antibacterial activity against Staphylococcus aureus and Salmonella enterica serotype Typhi. Both oils showed good to moderate activity against the tested pathogens. The significant nematicidal, insecticidal, herbicidal, antifungal, and antibacterial activities of both the essential oils might be helpful for the development of environmentally friendly pesticides that could be an alternative to synthetic pesticides in the future.     

Synthesis of Silver Nanoparticles from Extracts of Wild Ginger (Zingiber zerumbet) with Antibacterial Activity against Selective Multidrug Resistant Oral Bacteria

Antibiotic resistance rate is rising worldwide. Silver nanoparticles (AgNPs) are potent for fighting antimicrobial resistance (AMR), independently or synergistically. The purpose of this study was to prepare AgNPs using wild ginger extracts and to evaluate the antibacterial efficacy of these AgNPs against multidrug-resistant (MDR) Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis. AgNPs were synthesized using wild ginger extracts at room temperature through different parameters for optimization, i.e., pH and variable molar concentration. Synthesis of AgNPs was confirmed by UV/visible spectroscopy and further characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy analysis (EDXA), and Fourier-transform infrared spectroscopy (FTIR). Disc and agar well diffusion techniques were utilized to determine the in vitro antibacterial activity of plant extracts and AgNPs. The surface plasmon resonance peaks in absorption spectra for silver suspension showed the absorption maxima in the range of 400–420 nm. Functional biomolecules such as N–H, C–H, O–H, C–O, and C–O–C were present in Zingiber zerumbet (Z. zerumbet) (aqueous and organic extracts) responsible for the AgNP formation characterized by FTIR. The crystalline structure of ZZAE-AgCl-NPs and ZZEE-AgCl-NPs was displayed in the XRD analysis. SEM analysis revealed the surface morphology. The EDXA analysis also confirmed the element of silver. It was revealed that AgNPs were seemingly spherical in morphology. The biosynthesized AgNPs exhibited complete antibacterial activity against the tested MDR bacterial strains. This study indicates that AgNPs of wild ginger extracts exhibit potent antibacterial activity against MDR bacterial strains.     

Phytochemical Analysis,Antibacterial Activity and Modulating Effect of Essential Oil from Syzygium cumini (L.) Skeels

One of the main global problems that affect human health is the development of bacterial resistance to different drugs. As a result, the growing number of multidrug-resistant pathogens has contributed to an increase in resistant infections and represents a public health problem. The present work seeks to investigate the chemical composition and antibacterial activity of the essential oil of Syzygium cumini leaves. To identify its chemical composition, gas chromatography coupled to mass spectrometry was used. The antibacterial activity test was performed with the standard strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 25853 and Staphylococcus aureus ATCC 25923 and multidrug-resistant clinical isolates E. coli 06, P. aeruginosa 24 and S. aureus 10. The minimum inhibitory concentration (MIC) was determined by serial microdilution as well as the verification of the modulating effect of the antibiotic effect. In this test, the oil was used in a subinhibitory concentration. The test reading was performed after 24 h of incubation at 37 °C. The results show that the major chemical constituent is α-pinene (53.21%). The oil showed moderate activity against E. coli ATCC 25922, with the MIC of 512 µg/mL; there was no activity against the other strains. The oil potentiated the effect of antibiotics demonstrating possible synergism when associated with gentamicin, erythromycin and norfloxacin against E. coli 06 and S. aureus 10.     

Synthesis,Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido,Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives

A novel synthesis of thiazolo[2,3-b]quinazolines 4(a–e), pyrido[2′,3′:4,5]thiazolo[2,3-b]quinazolines {5(a–e), 6(a–e), and 7(a–e)}, pyrano[2′,3′:4,5]thiazolo[2,3-b]quinazolines 8(a–e), and benzo[4,5]thiazolo[2,3-b]quinazoloine9(a–e) derivatives starting from 2-(Bis-methylsulfanyl-methylene)-5,5-dimethyl-cyclohexane-1,3-dione 2 as efficient α,α dioxoketen dithioacetal is reported and the synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antibacterial agents against the bacterial strains, like S. aureus, E. coli, and P. aeruginosa. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 μg/mL while the others exhibited better antibacterial activity at 100 μg/mL. The results of this study showed that compound 6(c) possessed remarkable antibacterial activity, whereas compound 9(c) exhibited the highest efficacy as an antioxidant. The structures of the new synthetic compounds were elucidated by elemental analysis, IR, ¹H-NMR, and ¹³C-NMR.     

Phytochemical Investigation of Cordia africana Lam. Stem Bark: Molecular Simulation Approach

Background: The current work planned to evaluate Cordia africana Lam. stem bark, a traditionally used herb in curing of different ailments in Africa such as gastritis and wound infections, based on phytochemical and antibacterial studies of two pathogenic microorganisms: methicillin-resistant Staphylococcus aureus (MRSA) and Helicobacter pylori. Methods: High performance liquid chromatography (HPLC) profiling was used for qualitative and quantitative investigation of the ethanol extract. The minimum inhibitory concentration (MIC) of the ethanolic extract and isolated compounds was estimated using the broth microdilution method and evidenced by molecular dynamics simulations. Results: Four compounds were isolated and identified for the first time: α-amyrin, β-sitosterol, rosmarinic acid (RA) and methyl rosmarinate (MR). HPLC analysis illustrated that MR was the dominant phenolic acid. MR showed the best bacterial inhibitory activity against MRSA and H. pylori with MIC 7.81 ± 1.7 μg/mL and 31.25 ± 0.6, respectively, when compared to clarithromycin and vancomycin, respectively. Conclusion: The antibacterial activity of the stem bark of Cordia africana Lam. was evidenced against MRSA and H. pylori. Computational modeling of the studied enzyme-ligands systems reveals that RA and MR can potentially inhibit both MRSA peptidoglycan transpeptidases and H. pylori urease, thereby creating a pathway via the use of a double target approach in antibacterial treatment.     

Active Flavonoids from Colubrina greggii var. greggii S. Watson against Clinical Isolates of Candida spp.

Candida albicans is the most commonly implicated agent in invasive human fungal infections. The disease could be presented as minimal symptomatic candidemia or can be fulminant sepsis. Candidemia is associated with a high rate of mortality and high healthcare and hospitalization costs. The surveillance programs have reported the distribution of other Candida species reflecting the trends and antifungal susceptibilities. Previous studies have demonstrated that C. glabrata more frequently presents fluconazole-resistant strains. Extracts from Mexican plants have been reported with activity against pulmonary mycosis, among them Colubrina greggii. In the present study, extracts from the aerial parts (leaves, flowers, and fruits) of this plant were evaluated against clinical isolates of several species of Candida (C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis) by the broth microdilution assay. Through bioassay-guided fractionation, three antifungal glycosylated flavonoids were isolated and characterized. The isolated compounds showed antifungal activity only against C. glabrata resistant to fluconazole, and were non-toxic toward brine shrimp lethality bioassay and in vitro Vero cell line assay. The ethyl acetate and butanol extracts, as well as the fractions containing the mixture of flavonoids, were more active against Candida spp.     

Volatiles Composition and Antimicrobial Activities of Areca Nut Extracts Obtained by Simultaneous Distillation–Extraction and Headspace Solid-Phase Microextraction

The volatile components of areca nuts were isolated by headspace solid-phase microextraction (HS-SPME, DVB/CAR/PDMS fiber extraction) and simultaneous hydrodistillation–extraction (SHDE) and analyzed by gas chromatography/mass spectrometry. Furthermore, all SHDE fractions were tested for antimicrobial activity using the disk diffusion method on nine Gram-negative and Gram-positive bacteria (Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus canis, Streptococcus pyogenes, and Candida albicans). In total, 98 compounds (mainly alcohols, carbonyl compounds, fatty acids, esters, terpenes, terpenoids, and aliphatic hydrocarbons) were identified in SHDE fractions and by using SPME extraction Fatty acids were the main group of volatile constituents detected in all types of extracts. The microorganism most sensitive to the extract of the areca nut was Streptococcus canis. The results can provide essential information for the application of different treatments of areca nuts in the canning industry or as natural antibiotics.     

Detection of Volatiles by HS-SPME-GC/MS and Biological Effect Evaluation of Buddha’s Hand Fruit

The present work aimed to chemically characterize and evaluate the antiradical power and biological effects of Citrus medica var. sarcodactylus essential oil (EO) and hydrolate (Hy) from exocarp as well as methanol extracts, from both exocarp and mesocarp (EEX and MEX). The whole fresh fruit was also investigated by SPME-GC/MS to describe its volatile composition. EO and Hy were analyzed by GC/MS and HS-GC/MS techniques, respectively. Limonene and γ-terpinene were found to be the most abundant compounds both in the fresh parts of the fruit and in the EO, while α-terpineol and terpinen-4-ol were in the Hy. The extracts were also rich in furan and coumarin derivatives. A good antiradical activity of all samples except Hy was detected both against ABTS·+ than DPPH·, removed up to about 50%. The antibacterial activity against Bacillus cereus and Escherichia coli was evaluated by microwell dilution method to determine MIC and MBC values. EEX and MEX showed efficacy at very high concentrations against both tested bacteria. The MIC value of EO against B. cereus was 0.5% v/v, while Hy was not able to inhibit the bacterial growth at the tested concentrations. Cytotoxicity investigated on the HL60 leukemia cell line by MTT assay provided an EC₅₀ of 1.24% v/v for EO. Interesting activity of Hy was also observed.     

Synthesis,Antibacterial and Anthelmintic Activity of Novel 3-(3-Pyridyl)-oxazolidinone-5-methyl Ester Derivatives

In this study, a series of 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives was synthesized and characterized by ¹H NMR, ¹³C NMR, and LC-MS. The conducted screening antibacterial studies of the new 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives established that the methyl sulfonic acid esters have broad activity spectrum towards Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis and Staphylococcus epidermidis. Among them, compound 12e has the most potent activity, with an MIC of 16 μg/mL against B.subtilis, and could reduce the instantaneous growth rate of bacteria. Furthermore, molecular docking studies were also simulated for compound 12e to predict the specific binding mode of this compound. In addition, anthelmintic activity of these compounds was also evaluated against adult Indian earthworms (Pheretima posthuman). The results showed that compound 11b had the best effect. These results above can provide experimental reference for the development of novel antibacterial and anthelmintic drugs.     

Well-Orientation Strategy Biosynthesis of Cefuroxime-Silver Nanoantibiotic for Reinforced Biodentine™ and Its Dental Application against Streptococcus mutans

Dental caries results from the bacterial pathogen Streptococcus mutans (S. mutans) and is the maximum critical reason for caries formation. Consequently, the present study aims to evaluate the antibacterial activity of a newly synthesized nanoantibiotic–Biodentine formulation. The silver nanoparticles (ROE-AgNPs) were biosynthesized from the usage of Rosmarinus officinalis L. extract (ROE) and conjugated with cefuroxime to form Cefuroxime-ROE-AgNPs. Using Biodentine™ (BIOD), five groups of dental materials were prepared, in which Group A included conventional BIOD, Group B included BIOD with ROE-AgNPs, Groups C and D included BIOD with Cefuroxime-ROE-AgNPs at concentrations of 0.5% and 1.5% cefuroxime, respectively, and Group E included BIOD with 1.5% cefuroxime. The synthesized ROE-AgNPs or Cefuroxime-ROE-AgNPs were characterized for conjugating efficiency, morphology, particle size, and in vitro release. Minimum inhibitory concentration (MIC) of the cefuroxime, ROE-AgNPs, and Cefuroxime-ROE-AgNPs were additionally evaluated against cefuroxime resistant S. mutans, which furthered antibacterial efficacy of the five groups of dental materials. The UV-Visible spectrum showed the ROE-AgNPs or Cefuroxime-ROE-AgNPs peaks and their formation displayed through transmission electron microscopy (TEM), X-ray diffraction (XRD) pattern, and Fourier transforms infrared (FTIR) analysis. The end result of Cefuroxime-ROE-AgNPs showed conjugating efficiency up to 79%. Cefuroxime-ROE-AgNPs displayed the highest antibacterial efficacy against S. mutans as compared to cefuroxime or ROE-AgNPs alone. Moreover, the MIC of ROE-AgNPs and Cefuroxime-ROE-AgNPs was detected against S. mutans to be 25 and 8.5 μg/mL, respectively. Consequently, Cefuroxime-ROE-AgNPs displayed that a decrease in the MIC reached to more than three-fold less than MIC of ROE-AgNPs on the tested strain. Moreover, Cefuroxime-ROE-AgNPs/BIOD was employed as a novel dental material that showed maximum antimicrobial activity. Groups C and D of novel materials showed inhibitory zones of 19 and 26 mm, respectively, against S. mutans and showed high antimicrobial rates of 85.78% and 91.17%, respectively. These data reinforce the utility of conjugating cefuroxime with ROE-AgNPs to retrieve its efficiency against resistant S. mutant. Moreover, the nanoantibiotic delivered an advantageous antibacterial effect to BIOD, and this may open the door for future conjugation therapy of dental materials against bacteria that cause dental caries.     

Antimicrobial,Cytotoxic and Mutagenic Activity of Gemini QAS Derivatives of 1,4:3,6-Dianhydro-l-iditol

A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesized, using isommanide (1,4:3,6-dianhydro-d-mannitol) as a starting material. Both aromatic (pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), (3-carboxamide)pyridine; N-methylimidazole) and aliphatic (trimethylamine, N,N-dimethylhexylamine, N,N-dimethyloctylamine, N,N-dimethyldecylamine) amines were used, giving eight gemini quaternary ammonium salts (QAS). All salts were tested for their antimicrobial activity against yeasts, Candida albicans and Candida glabrata, as well as bacterial Staphylococcus aureus and Escherichia coli reference strains. Moreover, antibacterial activity against 20 isolates of S. aureus collected from patients with skin and soft tissue infections (n = 8) and strains derived from subclinical bovine mastitis milk samples (n = 12) were evaluated. Two QAS with octyl and decyl residues exhibited antimicrobial activity, whereas those with two decyl residues proved to be the most active against the tested pathogens, with MIC of 16–32, 32, and 8 µg/mL for yeast, E. coli, and S. aureus reference and clinical strains, respectively. Only QAS with decyl residues proved to be cytotoxic in MTT assay against human keratinocytes (HaCaT), IC₅₀ 12.8 ± 1.2 μg/mL. Ames test was used to assess the mutagenic potential of QAS, and none of them showed mutagenic activity in the concentration range 4–2000 µg/plate.     

In Vitro Investigation of the Impact of Bacterial–Fungal Interaction on Carbapenem-Resistant Klebsiella pneumoniae

Fungal–bacterial co-culturing is a potential technique for the production of secondary metabolites with antibacterial activity. Twenty-nine fungal species were screened in a co-culture with carbapenem-resistant Klebsiella pneumoniae at different temperatures. A temperature of 37 ° showed inhibition of bacterial growth. Antimicrobial susceptibility testing for K. pneumoniae was conducted to compare antibiotic resistance patterns before and after the co-culture. Genotypic comparison of the K. pneumonia was performed using next generation sequencing (NGS). It was shown that two out of five K. pneumoniae, with sequence type ST 101 isolates, lost bla-_OXA48, bla-_CTX-M-14, tir, strA and strB genes after the co-culture with Scopulariopsis brevicaulis fungus. The other three isolates (ST 383 and 147) were inhibited in the co-culture but did not show any changes in resistance. The total ethyl acetate extract of the fungal–bacterial co-culture was tested against K. pneumoniae using a disc diffusion method. The concentration of the crude extract was 0.97 mg/µL which resulted in total inhibition of the bacteria. Using chromatographic techniques, the purified compounds were identified as 11-octadecenoic acid, 2,4-Di-tert-butylphenol, 2,3-Butanediol and 9-octadecenamide. These were tested against K. pneumoniae using the well diffusion method at a concentration of 85 µg/µL which resulted in total inhibition of bacteria. The co-culture results indicated that bacteria under chemical stress showed variable responses and induced fungal secondary metabolites with antibacterial activities.