Beshanzoides A–D,unprecedented cycloheptanone-containing polyketides from Penicillium commune P-4-1, an endophytic fungus of the endangered conifer Abies beshanzuensis

A number of previously undescribed (1–7) and structurally related known (8–17) isobenzofuran-type polyketides were obtained from the fermentation of Penicillium commune P-4-1, an endophytic fungus isolated from the fresh trunk bark of the critically endangered conifer Abies beshanzuensis. Beshanzoides A–D (1–4, resp.) feature a cycloheptanone-containing isobenzofuran ring system hitherto unknown, which might be biosynthesized via two steps of aldol reactions starting from a common co-occurring isobenzofuran-type polyketide as the precursor. The new structures were elucidated by spectroscopic methods, electronic circular dichroism data, and single crystal X-ray diffraction analyses. Beshanzoide E (5) showed antimicrobial activity (MIC: 16 μg mL⁻¹) against Staphylococcus aureus, whereas (±)-strobide A (10) inhibited (MIC: 16 μg mL⁻¹) Candida albicans. Cyclopaldic acid (12) and 3-O-methyl-cyclopaldic acid (13) exhibited inhibitory effects against acetyl-CoA carboxylase 1 (ACC1) with IC₅₀ values of 0.96 and 11.77 μM, respectively. Compound 12 also inhibited (IC₅₀: 7.56 μM) ATP-citrate lyase (ACL).

Four unprecedented cycloheptanone-containing and some related known bioactive polyketides were isolated from an endophytic fungus associated with the critically endangered conifer Abies beshanzuensis.     

Inhibition of biofilm formation and quorum sensing mediated phenotypes by berberine in Pseudomonas aeruginosa and Salmonella typhimurium

Quorum sensing is involved in biofilm formation and modulates virulence factor production in pathogenic bacteria. Quorum sensing inhibitors can be used as novel intervention strategies for attenuating bacterial pathogenicity. Berberine is an isoquinoline alkaloid with pharmacological properties. The present study investigated the sub-inhibitory concentrations of berberine for inhibiting biofilm formation and quorum sensing regulated phenotypes in the bacterial pathogens Pseudomonas aeruginosa PA01 and Salmonella enterica serovar Typhimurium. Berberine inhibited quorum sensing regulated violacein production in C. violaceum. It reduced the pigment production in the wild type strain at 1.6 mg mL⁻¹ by 62.67%. In the opportunistic pathogen, P. aeruginosa PA01, at sub-MIC, it showed significant antibiofilm activity in by reducing biomass by 71.70% (p < 0.05). It prevented biofilm formation and inactivated biofilm maturation in bacterial pathogens at the concentration ranging from 0.019 to 1.25 mg mL⁻¹. In silico studies showed that berberine interacted with the quorum sensing signal receptors, LasR and RhlR. Furthermore, its anti-infective properties in S. Typhimurium were studied. At sub-inhibitory concentrations of 0.019 mg mL⁻¹, it reduced biofilm formation in S. Typhimurium by 31.20%. It significantly prevented invasion and adhesion of Salmonella invasion in the colonic cell, HT 29 by 55.37% and 54.68%, respectively. It was capable of reducing in vivo virulence in Caenorhabditis elegans infected with Salmonella at 0.038 mg mL⁻¹ by 65.38%. Our results suggest that berberine, previously recognised for its antimicrobial activity, could find potential application as an anti-biofilm and anti-infective agent based on its quorum sensing inhibitory activity.

Quorum sensing regulates violacein pigment production in C. violaceum.     

New dimeric chromanone derivatives from the mutant strains of Penicillium oxalicum and their bioactivities

Three new chromanone dimer derivatives, paecilins F–H (1–3) and ten known compounds (4–13), were obtained from the mutant strains of Penicillium oxalicum 114-2. Their structures were elucidated by extensive analysis of spectroscopic data and comparison with reported data, and the configurations of 1–3 were resolved by quantum chemical calculations of NMR shifts and ECD spectra. Compounds 5 and 11 showed significant anti-influenza A virus activities with IC₅₀ values of 5.6 and 6.9 μM, respectively. Compounds 8 and 9 displayed cytotoxic activities against the MIA-PaCa-2 cell line with IC₅₀ values of 2.6 and 2.1 μM, respectively. Compound 10 exhibited antibacterial activities against Bacillus cereus with a MIC value of 4 μg mL⁻¹.

Three new chromanone dimers, paecilins F–H (1–3) and ten known compounds (4–13), were obtained from the mutant strains of Penicillium oxalicum 114-2, and some of them showed significant antiviral activities.     

UPLC-MS-guided isolation of single ether linkage dimeric 2-(2-phenylethyl)chromones from Aquilaria sinensis

Eleven novel uncommon single ether linkage dimeric 2-(2-phenylethyl)chromones (aquilasinenones A–K) were isolated by a UPLC-MS guided method from artificial hole-induced agarwood originating from Aquilaria sinensis. Their structures were unambiguously deduced using HRESIMS data, detailed 1D and 2D NMR spectroscopic analysis, and experimental ECD spectra. All the compounds were tested for acetylcholinesterase (AChE) inhibitory activity by Ellman''s colorimetric method, and compounds 9–11 displayed weak AChE inhibitory activity with the inhibition ranging from 15.6% to 16.8% at a concentration of 50 μg mL⁻¹.

Eleven novel uncommon single ether linkage dimeric 2-(2-phenylethyl)chromones (aquilasinenones A–K) were isolated by a UPLC-MS guided method from artificial hole-induced agarwood originating from Aquilaria sinensis.     

Photo-induced synthesis,structure and in vitro bioactivity of a natural cyclic peptide Yunnanin A analog

A cyclic analog of natural peptide Yunnanin A was synthesized via photoinduced single electron transfer reaction (SET) in the paper. The resulting compound exhibited potent bioactivity (with IC₅₀ values 29.25 μg mL⁻¹ against HepG-2 cell lines and 65.01 μg mL⁻¹ against HeLa cell lines), but almost have no toxicity to normal cells (with IC₅₀ values 203.25 μg mL⁻¹ against L929 cell lines), which may be served as a potential antitumor drug for medical treatment. The spatial structure was examined by experimental electronic circular dichroism (ECD) and quantum chemistry calculations. Moreover, the theoretical study suggested that special intramolecular hydrogen bonds and γ, β-turn secondary structures may be possible sources affecting cyclic peptide''s bioactivity.

The photo-induced synthesis, structure and in vitro bioactivity study of a Yunnanin A cyclopeptide analog was presented.     

Silver nanoparticle@carbon quantum dot composite as an antibacterial agent

A AgNPs@S,N-CQDs composite was synthesized by a one-step approach. It possessed AgNPs naturally surrounded by S,N-CQDs, and the size of the particles was found to be uniform and stable via a series of characterization methods. The antibacterial properties of the composite material were studied, and it had good antibacterial properties against S. aureus, E. coli, MRSA and C. albicans. The minimum inhibitory concentrations were 63 μg mL⁻¹ against S. aureus and MRSA and 32 μg mL⁻¹ against E. coli and C. albicans. In addition, the AgNPs@S,N-CQDs composite had an antibacterial effect via the generation of ROS, which was verified using the DCFH-DA kit. Finally, HepG2 cells were used to study its biocompatibility. The antibacterial properties and biocompatibility results show that the AgNPs@S,N-CQDs composite material can serve as a promising antibacterial agent.

Synthesis of AgNPs@S,N-CQDs active against bacteria.     

Rigid 3D-spiro chromanone as a crux for efficient antimicrobial agents: synthesis,biological and computational evaluation

The development of new and effective antimicrobial agents with novel chemical skeletons and working mechanisms is highly desirable due to the increased number of resistant microbes. Different new compounds based upon a 3D-spiro chromanone scaffold such as Mannich bases 2 and 3 in addition to azo dye 4 were synthesized. Besides, the condensation reactions of the hydrazide-spiro chromanone 8 with different ketonic reagents led to the synthesis of pyrazoles (9 & 10) and anils (11 & 13). Moreover, the methoxyl substituted spiro chromanone 14 was condensed with different hydrazines and hydrazides to give the corresponding hydrazones 15–18 in up to 85% yields. The condensation of the hydrazone 18 with salicylaldehyde yielded coumarinyl spiro chromanone 19 in an excellent yield, whereas its reaction with benzaldehyde followed by hydrazine afforded aminopyrazole derivative 21 in 82% yield. The antimicrobial evaluation suggested that hydrazide 8 has a substantial activity against different microbes (S. aureus: D = 22 mm, MIC = 1.64 μM; E. coli: D = 19 mm, MIC = 1.64 μM; C. albicans: D = 20 mm, MIC = 6.57 μM). Moreover, promising antimicrobial activities were observed for azo dye 4 (D = 13–19 mm, MIC = 5.95–11.89 μM), hydrazone 17 (D = 17–23 mm, MIC = 1.88–3.75 μM), and aminopyrazole 21 (D = 14–19 mm, MIC = 2.24–8.98 μM). The molecular docking revealed that compounds 4, 8, 17, and 21 had good to high binding affinities with different microbial targets such as penicillin-binding proteins (−7.4 to −9.9 kcal), DNA gyrase (−7.8 to −9.0 kcal), lanosterol 14-alpha demethylase (−8.2 to −11.2 kcal), and exo-beta-1,3-glucanase (−8.2 to −11.9 kcal). The QSAR analysis ascertained a good correlation between the antimicrobial activity of 3D-spiro chromanone derivatives and their structural and/or physicochemical parameters.

New heterocyclic compounds based upon rigid 3D-spiro chromanone scaffold have been synthesized and evaluated as efficient antimicrobial agents. Molecular docking and QSAR have explained and supported the observed promising antimicrobial activity.     

The use of polyhydroxylated carboxylic acids and lactones to diminish biofilm formation of the pathogenic yeast Candida albicans

The vaginal microbiome of healthy women is a diverse and dynamic system of various microorganisms. Any sudden change in microbe composition can increase the vaginal pH and thus lead to vaginal infections, conditions that affect a large percentage of women each year. The most common fungal strains involved in infections belong to the yeast species Candida albicans. The main virulence factor of C. albicans is the ability to transform from planktonic yeast-form cells into a filamentous form (hyphae or pseudohyphae), with the subsequent formation of biofilm. The hyphal form, constituted by filamentous cells, has the ability to invade tissue and induce inflammation. Our hypothesis is that certain polyhydroxylated carboxylic acids, that may serve as an alternative carbohydrate source and at the same time lower the pH, function as an indicator of a nutrient-rich environment for C. albicans, which favors planktonic cells over hyphae, and thus diminish the formation of biofilm. We have shown that the biofilm formation in C. albicans and other Candida species can be significantly reduced by the addition of glucono-δ-lactone (GDL).

Treatment of Candida albicans with glucono δ-lactone results in less formation of hyphae and diminish biofilm formation.     

Design,synthesis, bio-evaluation,and in silico studies of some N-substituted 6-(chloro/nitro)-1H-benzimidazole derivatives as antimicrobial and anticancer agents

A new series of 6-substituted 1H-benzimidazole derivatives were synthesized by reacting various substituted aromatic aldehydes with 4-nitro-o-phenylenediamine and 4-chloro-o-phenylenediamine through condensation using sodium metabisulfite as the oxidative reagent. The N-substituted 6-(chloro/nitro)-1H-benzimidazole derivatives were prepared from the 6-substituted 1H-benzimidazole derivatives and substituted halides using potassium carbonate by conventional methods as well as by exposure to microwave irradiation. Seventy-six 1H-benzimidazole derivatives have been synthesized in moderate to excellent yields with the microwave-assisted method (40 to 99%). Compounds 1d, 2d, 3s, 4b, and 4k showed potent antibacterial activity against Escherichia coli, Streptococcus faecalis, MSSA (methicillin-susceptible strains of Staphylococcus aureus), and MRSA (methicillin-resistant strains of Staphylococcus aureus) with MIC (the minimum inhibitory concentration) ranging between 2 and 16 μg mL⁻¹ as compared to ciprofloxacin (MIC = 8–16 μg mL⁻¹), in particular compound 4k exhibits potent fungal activity against Candida albicans and Aspergillus niger with MIC ranging between 8 and 16 μg mL⁻¹ compared with the standard drug fluconazole (MIC = 4–128 μg mL⁻¹). In addition, compounds 1d, 2d, 3s, 4b, and 4k also showed the strongest anticancer activity among the synthesized compounds against five tested cell lines with IC₅₀ (half-maximal inhibitory concentration) ranging between 1.84 and 10.28 μg mL⁻¹, comparable to paclitaxel (IC₅₀ = 1.38–6.13 μM). Furthermore, the five most active compounds showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile in comparison to ciprofloxacin, fluconazole, and paclitaxel as reference drugs. Molecular docking predicted that dihydrofolate reductase protein from Staphylococcus aureus is the most suitable target for both antimicrobial and anticancer activities, and vascular endothelial growth factor receptor 2 and histone deacetylase 6 are the most suitable targets for anticancer activity of these potent compounds.

The purpose of this study is to synthesize novel N-substituted 6-(chloro/nitro)-1H-benzimidazole derivatives with various substituted aryl groups at position 2 and alkylation at position 1, and evaluate their antimicrobial and anticancer activities.     

Study on microwave assisted extraction of chrysophanol and its intervention in biofilm formation of Streptococcus suis

A microwave assisted extraction technology was used to extract chrysophanol from rhubarb. The present study will focus on the optimum extraction conditions of chrysophanol and discuss the inhibitory effect of chrysophanol on the biofilm formation of Streptococcus suis (S. suis). A Box–Behnken design based on single-factor experiments was applied to optimize the microwave assisted extraction process and to study the factors'' relationships with each other. The results showed that a microwave temperature of 56 °C, ethanol concentration of 70%, microwave power of 540 W and liquid to raw material ratio of 55 mL g⁻¹ were the optimal conditions for the microwave method. The yield of chrysophanol was 2.54 ± 0.07% under the optimal conditions, which was in agreement with the predicted value (2.64%). Then, the chemical structure of the extracted chrysophanol was identified by LC-MS. In addition, in vitro experiments showed that chrysophanol has an inhibitory effect on S. suis (minimum inhibitory concentration was 1.98 μg mL⁻¹) and was shown to significantly inhibit the capability of S. suis to form a biofilm using crystal violet staining. Finally, scanning electron microscopy analysis showed that the three-dimensional structure of the biofilm deposited by the S. suis community was destroyed by chrysophanol.

A microwave assisted extraction technology was used to extract chrysophanol from rhubarb.     

The antioxidant and tyrosinase inhibition properties of essential oil from the peel of Chinese Torreya grandis Fort.

The antioxidant and tyrosinase inhibition properties of essential oil from the peel of Chinese Torreya grandis Fort. (CTGF oil) were investigated. The antioxidant properties of CTGF oil were evaluated via 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging tests, and it showed an IC₅₀ value of 0.88 ± 0.06 μg mL⁻¹ compared to V_C with a value of 1.0 ± 0.1 μg mL⁻¹ and BHT with a value of 2.9 ± 0.1 μg mL⁻¹. CTGF oil had relatively significant DPPH scavenging activity (p < 0.05), which could be compared to other natural oils as follows: cassia oil (92.4%) > peppermint oil (89.1%) > clove leaf oil (87.7%) > nutmeg oil (80.1%) > CTGF oil (42.6%) > lemon oil (25.5%). Furthermore, changes in the peroxide values of different treatment groups during storage for 60 days were estimated. CTGF oil displayed better antioxidant activity than lemon oil, with activity similar to that of BHT for the reduction of the peroxide value. Moreover, CTGF oil effectively inhibited the oxidation of 3,4-dihydroxy-l-phenylalanine (l-DOPA) through tyrosinase (P < 0.05). The essential oil obtained after hydrodistillation from the peel of Chinese Torreya grandis Fort. could be potentially utilized as a good new alternative source of natural antioxidants for the food and cosmetics industries.

The antioxidant and tyrosinase inhibition properties of essential oil from the peel of Chinese Torreya grandis Fort. (CTGF oil) were investigated.     

How the change of OMe substituent position affects the performance of spiro-OMeTAD in neutral and oxidized forms: theoretical approaches

Density functional theory (DFT) was used to investigate the electronic and optical properties of the ortho, meta, and para derivatives of 2,2′,7,7′-tetrakis-(N,N-di-4-methoxyphenylamino)-9,9′spirobifluorene (spiro-OMeTAD) and its two oxidized forms (+1 and +2). The energy level, distribution shape, and density of highest occupied molecular orbital (HOMO) and of lowest unoccupied molecular orbital (LUMO) were computed for all three derivatives and compared in the neutral and oxidized forms. Results indicated that the different positions of OMe in the spiro-OMeTAD framework lead to different optical properties. It was also found that compared to the neutral form, in the oxidized forms, the maximum absorption band red shifts, new signals in the visible range between 500 and 850 nm appear, and the Stokes shift values reduce for all three derivatives. The exciton binding energy of spiro-OMeTAD with an o-OMe substituent is 0.52 eV, being smaller than that of p-OMe and m-OMe, indicating easier generation of free charge carriers. The hole mobility was calculated for all three molecules, and the obtained data revealed that the hole mobility of the o-OMe substituent has a value of 7.90 × 10⁻³ cm² V⁻¹ s⁻¹, which is respectively 3 and 11 times larger than that of p-OMe and m-OMe. The smaller exciton binding energy and larger hole mobility of the o-OMe substituent will result in a higher short-circuit current density (J_sc) and a higher fill factor, respectively, demonstrating that po-spiro-OMeTAD is a promising candidate for use in perovskite solar cells. The reorganization energy, electron affinity, and ionization potential were also calculated and discussed.

Effect of changing the position of OMe substituent on the electrochemical and optical properties of spiro-MeOTAD hole conductor in neutral and oxidized forms for use in perovskite solar cells.     

Unravelling the antifungal and antiprotozoal activities and LC-MS/MS quantification of steroidal saponins isolated from Panicum turgidum

Bioassay-guided investigation of Panicum turgidum extract resulted in the identification of seven steroidal saponins (Turgidosterones 1–7). They were evaluated for their in vitro antifungal, antileishmanial, and antitrypanosomal activities. Turgidosterone 6 was the most active antifungal against Candida albicans and Candida neoformans (IC₅₀ values of 2.84 and 1.08 μg mL⁻¹, respectively). Turgidosterones 4–7 displayed antileishmanial activity against Leishmania donovani promastigotes with IC₅₀ values ranging from 4.95 to 8.03 μg mL⁻¹ and against Leishmania donovani amastigote/THP with IC₅₀ values range of 4.50–9.29 μg mL⁻¹. Activity against Trypanosoma brucei was also observed for Turgidosterones 4–7 with an IC₅₀ values range of 1.26–3.77 μg mL⁻¹. Turgidosterones 1–3 did not display any activity against the tested pathogens. The study of structure–activity relationships of the isolated saponins indicated that the antifungal, antileishmanial, and antitrypanosomal activities are markedly affected by the presence of spirostane-type saponins and the elongation of the sugar residue at C-3. To quantitatively determine the most abundant active ingredient in Panicum turgidum extract, a single run, sensitive, and highly selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been applied under positive and negative modes. The obtained results showed that compound 5 was the most abundant (95.93 ± 1.10 mg per gram of dry Panicum turgidum extract), followed by 6 (52.51 ± 1.05 mg gm⁻¹), 4 (32.71 ± 0.48 mg gm⁻¹), and 7 (13.19 ± 0.50 mg gm⁻¹). Docking of these saponins against the Candida albicans oxidoreductases and Leishmania infantum trypanothione reductase active sites revealed their potential to effectively bind with a number of key residues in both receptor targets.

Bioassay-guided investigation of Panicum turgidum extract resulted in the identification of seven steroidal saponins (Turgidosterones 1–7).     

Preparation of terpolymer capsules containing Rosmarinus officinalis essential oil and evaluation of its antifungal activity

The essential oil from Rosmarinus officinalis presents antifungal activity and is used in industry as a natural preserving agent. However, essential oils are unstable compounds. So, the encapsulation of essential oils is a technique used to protect it, minimizing degradation and reducing undesired interaction with the other formulation components. Thus, this work focuses on the synthesis of terpolymeric capsules containing essential oil from Rosmarinus officinalis, aiming to use it as an antifungal component in cosmetics. The capsules were obtained via terpolymerization of methyl methacrylate, styrene and methacrylic acid in a dispersed phase polymerization process. The properties of the polymers and the fungicide activity were evaluated. The studied essential oil presented a Minimum Inhibitory Concentration (MIC) ranging from 2.25 to 4.5 mg mL⁻¹ and a Minimum Fungicidal Concentration (MFC) from 4.5 to 9.0 mg mL⁻¹ for strains of Candida albicans, Candida glabrata and Candida parapsilosis, and after the encapsulation process, the antifungal activity of the oil was maintained. Additionally, cytotoxicity assays against fibroblast cell lines and human keratinocytes showed that the polymeric nanocapsules containing Rosmarinus officinalis essential oil can be regarded as a very promising material intended for cosmetics and drug delivery applications.

The essential oil from Rosmarinus officinalis presents antifungal activity and is used in industry as a natural preserving agent. However, essential oils are unstable compounds.     

Heptaketides from the endophytic fungus Pleosporales sp. F46 and their antifungal and cytotoxic activities

Six new heptaketides, pleosporalins A–F (1–5, and 7), and a new heptaketide derivative, pleosporalin G (9), together with four biosynthetically related known compounds (6, 8, 10, and 11), were isolated from an endophytic fungus, Pleosporales sp. F46, found in the medicinal plant Mahonia fortunei. The structures and stereochemistry of these compounds were established by extensive spectroscopic analyses including LC-HRMS, NMR spectroscopy, optical rotations, ECD calculations, and single-crystal X-ray diffraction. The antifungal activities of isolated compounds 1–11 were investigated against Candida albicans, and their cytotoxic activities were evaluated against A549, SMMC-721, and MDA-MB-231 cancer cell lines. Compound 1 was active against C. albicans with an MIC₈₀ of 128 μg mL⁻¹, and compound 7 showed moderate cytotoxicity against MDA-MB-231 with an IC₅₀ of 22.4 ± 1.1 μM. By comparing compounds 1 and 7 with structurally related metabolites, it was revealed that alterations to their C-1 or C-2 substitutions could significantly influence their antifungal or cytotoxic efficacies.

New bioactive heptaketide derivatives were isolated and characterized from an endophytic fungus, Pleosporales sp. F46.     

Effect of metabolic uncoupler, 3,3′,4′,5-tetrachlorosalicylanilide (TCS) on Bacillus subtilis: biofilm formation,flocculability and surface characteristics

In order to understand the inhibitory mechanism of metabolic uncoupler in biofilm, this study investigated the effect of TCS on B. subtilis biofilm formation, flocculability, surface characteristics and thermodynamic properties. An optimal concentration of TCS, a metabolic uncoupler, was observed to substantially inhibit biofilm formation and the secretion of extracellular polymeric substances (EPS). The effect of TCS on the zeta potential and flocculability of bacterial suspension implied the addition of 100 μg L⁻¹ TCS increased the net negative charge of cell surface which induced the reduction of B. subtilis flocculability. Meanwhile, the effects of TCS on bacterial surfacial thermodynamic properties were analyzed by the Derjaguin–Landau–Verwey–Overbeek (DLVO) and extend DLVO (XDLVO) theories. As DLVO and XDLVO predicted, the primary energy barrier between bacterial cells incubated with 100 μg L⁻¹ TCS were increased compared to that of control, indicating that B. subtilis incubated with 100 μg L⁻¹ TCS must consume more energy to aggregate or form biofilm.

This study aimed to investigate the inhibitory mechanism of metabolic uncoupler on biofilm formation through surface characteristics and thermodynamics analysis.     

Novel chalcone derivatives containing a 1,2,4-triazine moiety: design,synthesis, antibacterial and antiviral activities

A series of novel chalcone derivatives containing the 1,2,4-triazine moiety were synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR and elemental analyses. Antiviral bioassays revealed that most of the compounds exhibited good antiviral activity against tobacco mosaic virus (TMV) at a concentration of 500 μg mL⁻¹. The designated compound 4l was 50% effective in terms of curative and protective activities against TMV with 50% effective concentrations (EC₅₀) of 10.9 and 79.4 μg mL⁻¹, which were better than those of ningnanmycin (81.4 and 82.2 μg mL⁻¹). Microscale thermophoresis (MST) also showed that the binding of compound 4l to coat protein (TMV-CP) yielded a K_d value of 0.275 ± 0.160 μmol L⁻¹, which was better than that of ningnanmycin (0.523 ± 0.250 μmol L⁻¹). At the same time, molecular docking studies for 4l with TMV-CP (PDB code:1EI7) showed that the compound was embedded well in the pocket between the two subunits of TMV-CP. Meanwhile, compound 4a demonstrated excellent antibacterial activities against Ralstonia solanacearum (R. solanacearum), with an EC₅₀ value of 0.1 μg mL⁻¹, which was better than that of thiodiazole-copper (36.1 μg mL⁻¹) and bismerthiazol (49.5 μg mL⁻¹). The compounds act by causing folding and deformation of the bacterial cell membrane as observed using scanning electron microscopy (SEM). The chalcone derivatives thus synthesized could become potential alternative templates for novel antiviral and antibacterial agents.

A series of novel chalcone derivatives containing the 1,2,4-triazine moiety were synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR and elemental analyses.     

A new strategy for synthesizing silver doped mesoporous bioactive glass fibers and their bioactivity,antibacterial activity and drug loading performance

A new strategy for preparing mesoporous metal-doped bioactive glass fibers (MBGFs) was designed, which included electrospinning and sulfonating mesoporous PS fibers, precipitating metal ions and bioactive glass sol–gel precursor into the mesoporous polystyrene (PS) fibers and calcinations. Silver-doped mesoporous BGFs (Ag-MBGFs) with a uniform diameter of 1–2 μm and a specific surface area of 40.22 m² g⁻¹ were prepared as an example and characterized by SEM, XRD, TG, ICP and FTIR. These Ag-MBGFs showed excellent bioactivity, antibacterial properties and drug loading and release performance due to their special mesoporous and fibrous structure. The concentration of Staphylococcus aureus decreased from 1 × 10⁸ colony-forming units per mL (CFU mL⁻¹) to 2.5 × 10⁶ CFU mL⁻¹ in 2 h and then to 2 × 10² CFU mL⁻¹ in 12 h when the concentration of the Ag-MBGFs reached 16 mg mL⁻¹. BGFs of different compositions and functions could be prepared by the same strategy in a mesoporous PS fiber template, which could enrich materials for constructing orthopedic implants.

A new strategy for preparing mesoporous metal-doped bioactive glass fibers.     

tert-Butylphenylthiazoles with an oxadiazole linker: a novel orally bioavailable class of antibiotics exhibiting antibiofilm activity

The structure–activity and structure–kinetic relationships of a new tert-butylphenylthiazole series with oxadiazole linkers were conducted with the objective of obtaining a new orally available antibacterial compounds. Twenty-two new compounds were prepared, purified and identified. Their activity against methicillin-resistant Staphylococcus aureus were examined. Compound 20 with 3-hydroxyazetidine as a nitrogenous side chain showed promising activity against twenty-four clinical isolates, including vancomycin-resistant staphylococcal and enterococcal species with MIC values ranging from 4–8 μg mL⁻¹. Additional advantages of this compound include an ability to eradicate staphylococcal biofilm mass in a dose-dependent manner as well as high metabolic stability after an oral dose of 25 mg kg⁻¹ with a biological half-life that exceeds 5 hours and a plasma concentration (C_max) that exceeds the MIC values.

The structure–activity and structure–kinetic relationships of a new tert-butylphenylthiazole series with oxadiazole linkers were conducted with the objective of obtaining a new orally available antibacterial compounds.     

A ratiometric fluorescence sensor based on enzymatically activatable micellization of TPE derivatives for quantitative detection of alkaline phosphatase activity in serum

A novel ratiometric fluorescence assay via enzymatically activatable micellization in aqueous solution was devised for quantitative detection of alkaline phosphatase (ALP) activity. We demonstrated that the dephosphorylation of the water-soluble, phosphate-functionalized, fluorophore monomer P-TPE-TG, induced by an enzymatic reaction of ALP, leads to micelle formation in aqueous solution because its water-soluble functionality is reduced. The dephosphorylation-induced micellization of P-TPE-TG exhibited a ratiometric sensing response for various ALP concentrations (10–200 mU mL⁻¹) and provided a suitable sensing platform for naked eye detection with increased fluorescence quantum yield (Φ = 3.2%), even compared to a typical TPE-based sensor (Φ = 1.0%), where ALP can be sensed with a detection limit of 0.034 mU mL⁻¹. In addition, P-TPE-TG displayed excellent sensing performance at concentrations from 0 to 50 mU mL⁻¹ in diluted human serum (10%), which offers the capability to exploit ratiometric responses for bioactive substances under practical conditions.

A novel ratiometric fluorescence assay via enzymatically activatable micellization in aqueous solution was devised for quantitative detection of alkaline phosphatase (ALP) activity.