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OBJECTIVE: The growing bacterial resistance towards classical antibiotics demands the development of novel approaches for the effective treatment of potentially fatal bacterial infections in humans. Proteostasis is crucial for the survival of every living cell, as several important physiological functions depend on well-regulated proteostasis. Within bacteria, the regulation of proteostasis relies on AAA+ (Adenosine 5'-triphosphatases associated with diverse cellular activities), ATPases, such as the HslVU complex (heat shock locus gene products U and V), along with other proteases. The HslVU protease/chaperon complex is thought to be the progenitor of the eukaryotic proteasome that regulates proteostasis mostly in prokaryotes. This study aimed to determine the inhibitory potential of 3-substituted coumarin derivatives against Escherichia coli heat shock locus V (HslV) protease. MATERIALS AND METHODS: In this study, twenty-three derivatives of 3-substituted coumarin were assessed for their inhibitory potential against E. coli HslV protease using both in-vitro and in-silico techniques. RESULTS: Among all the tested compounds, US-I-64, US-I-66, US-I-67, and US-I-68 displayed notable inhibitory potential against the HslV protease, showing IC50 (half maximal inhibitory concentration) values ranging from 0.2 to 0.73 µM. Additionally, the inhibitory potential of these compounds against the eukaryotic proteasome was also evaluated using a separate in-silico study. It was found that these compounds did not bind with the proteasomal active site, suggesting no apparent side effects of these lead molecules. CONCLUSIONS: These identified HslV protease inhibitors can be used for the development of novel and safer anti-bacterial drugs. [ABSTRACT FROM AUTHOR]

A series of novel 2,4,5‐trisubstituted imidazole motifs have been synthesized by a magnetically‐tuned halloysite‐supported sulfonic acid catalyst. The prepared supported sulfonic acid catalyst was well characterized by High‐resolution transmission electron microscopy (HR‐TEM), Scanning electron microscopy (SEM), Energy dispersive X‐rays spectroscopy (EDS), Fourier transform infrared (FTIR), X‐ray powder diffraction (XRD), Thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET), and Vibrating–sample magnetometry (VSM) techniques; and compounds were confirmed by 1H, 13C‐Nuclear magnetic resonance (NMR) and High resolution mass spectrometry (HRMS) techniques. The purity of compounds was established by High performance liquid chromatography (HPLC). All the prepared compounds were screened for their in vitro antidiabetic activity by using α‐amylase and α‐glucosidase inhibition assay taking acarbose as a reference standard and were found to exhibit significant α‐amylase inhibitory potentials, whereas for α‐glucosidase inhibition, compounds were equipotent to the reference standard. Compound bearing ferrocene moiety was identified as the strongest α‐amylase inhibitor of the series with IC50=47.83±0.63 μM, a five‐fold more potency compared to acarbose (IC50 =269.39±0.29 μM). The presence of substituents in the second position of imidazole pharmacophore plays a key role in inhibitory activity. To find the possible binding interaction of compounds, in silico molecular docking study was performed. [ABSTRACT FROM AUTHOR]

Bacterial resistance to antibiotics and host defense systems is primarily due to bacterial biofilm formation in antibiotic therapy. In the present study, two complexes, bis (biphenyl acetate) bipyridine Cu (II) (1) and bis (biphenyl acetate) bipyridine Zn (II) (2), were tested for their ability to prevent biofilm formation. The minimum inhibitory concentration and minimum bactericidal concentration of complexes 1 and 2 were 46.87 ± 1.822 and 93.75 ± 1.345 and 47.87 ± 1.345 and 94.85 ± 1.466 μg/mL, respectively. The significant activity of both complexes was attributed to the damage caused at the membrane level and was confirmed using an imaging technique. The biofilm inhibitory potential levels of complexes 1 and 2 were 95% and 71%, respectively, while the biofilm eradication potential levels were 95% and 35%, respectively, for both complexes. Both the complexes showed good interactions with the E. coli DNA. Thus, complexes 1 and 2 are good antibiofilm agents that exert their bactericidal actions possibly by disrupting the bacterial membrane and interacting with the bacterial DNA, which can act as a powerful agent to restrain the development of bacterial biofilm on therapeutic implants. [ABSTRACT FROM AUTHOR]

The hydro-distilled leaves of Pistacia lentiscus are considered as an agricultural residue and of no commercial value yet. In this study, chromatographic purification of a methanolic fraction of P. lentiscus L. (lentisk) distilled leaves yielded pure compounds, including Quercitrin (QUE) and Loliolid (LOL) which are characterized, for the first time, in the lentisk leaves' residue. The inhibitory potential of QUE and LOL was investigated against tyrosinase and acetylcholinesterase activities using enzymatic assays and lysozyme fibrillation through Thioflavin-T fluorescence assay. Their binding mode to Bovine Serum Albumin (BSA) was also assessed by several spectroscopic analyses. Results show that QUE was more potent to inhibit enzyme activity than LOL. Besides, the Thioflavin-T assay confirmed that only QUE was able to block the fibril formation at a concentration of 25 µg/mL. Furthermore, the BSA quenching mechanism by QUE and LOL is a static process with conformational changes in BSA. Interestingly, our findings may provide novel insights into the potentiality of lentisk to be used as a bioresource for the generation of Quercitrin and Loliolid which can be commercially exploited in the field of cosmeceuticals and nutraceuticals. [ABSTRACT FROM AUTHOR]

Abstract: Antifungal activity of essential oils (EOs) of Zataria multiflora (thyme) and Syzygium aromaticum (clove) against Aspergillus flavus growth and aflatoxin B1 production was studied in potato dextrose agar (PDA) and potato dextrose broth (PDB), as well as in Iranian white cheese as a food model. The results showed that the inhibitory potential of EOs in the PDB medium is more than PDA medium. Clove EO on PDB medium prevented fungal growth and aflatoxin B1 production at 300 and 100 ppm, respectively. However, the thyme EO was not able to inhibit fungal growth completely and showed the strongest inhibition effect at 400 ppm. EOs also had more inhibitory activity in laboratory culture media than the food environments. EOs in all concentrations reduced aflatoxin B1 production and fungal growth in cheese, but only the clove EO at 150 ppm was able to prevent the fungal growth and aflatoxin B1 production completely. Thyme EO reduced aflatoxin B1 value to below detection threshold (2 ppb) at 10 μl. Our findings propose EOs as a natural inhibitor to control fungal contamination of foodstuffs such as Iranian white cheese. [ABSTRACT FROM AUTHOR]

The objectives of this study were to analyze phytochemical content of bawang hutan bulbs extract (Eleutherine palmifolia) and to test the inhibitory potential of bawang hutan bulbs extract on the growth of Vibrio harveyi bacteria at different doses. This study was conducted in March-May 2017 in Testing Laboratory of Fisheries and Marine Science Faculty of Halu Oleo University and Laboratory of Fish Health of Aquaculture Department of Fisheries and Marine Science Faculty and Laboratory of Biopharmaca of Bogor Agricultural University. Test parameter included: (1) Phytochemical test through the method of color visualization, (2) Inhibitory potential test using two methods namely agar diffusion and co-culture. Treatment of dose consisted of positive control/K+ (Chloramphenicol 30 mg/ml), negative control/K- (Sterile Aquadest) and treatment of extract included A (20 mg/ml), B (40 mg/ml), C (60 mg/ml), D (80 mg/ml). Qualitatively, result of phytochemical test showed that bawang hutan bulbs extract contained flavonoid, tannin, saponin, quinone, steroid and triterpenoid compounds. Result of inhibitory potential test indicated that treatment D obtained the highest inhibitory potential, while the minimum inhibitory potential was found in treatment A. The best co-culture test result was also found in treatment D, in which 24 hours after co-culture was performed, no V. harveyi colonies (total bacteria of 0 CFU/mL) were found. Bawang hutan bulbs extract in this study was able to inhibit the growth of V. harveyi.

Introduction: Gout is a systemic disorder which usually affects the joints of the body system with an increased incidence rate in the elderly people. The cause for gout is accumulation of uric acid in the body. Elimination of the uric acid crystals is done by inhibition of xanthine oxidase (XO) which is responsible for the conversion of xanthine to uric acid. Here, we have preferred the plant extract Solanum virginianum for XO inhibition which is said to have more expectorant properties with least side effects. Materials and Methods: The study included preparation of the plant extract and XO inhibitory activity was measured spectrophotometrically based on the procedure reported by Nguyen et al. and was compared with the standard drug allopurinol. Results: The inhibitory potential of the plant extract against XO activity is increasing with increasing concentration with its maximum of 60.8% obtained at 100 μg/ml. Conclusion: S. virginianum has a significant effect against the XO activity and, hence, can be preferred for the future uses in the prognosis of gout as it has less side effects when compared to the corticosteroids. [ABSTRACT FROM AUTHOR]

This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut (Castanea crenata Sieb. et Zucc), a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli (barnyardgrass), Lactuca sativa (lettuce), and Raphanus sativus (radish). Laboratory and greenhouse trials showed that leaves of C. crenata appeared as a promising material to manage weeds, especially the dicot weeds. By GC-MS and HPLC analyses, gallic, protocatechuic, p-hydroxybenzoic, caffeic, ferulic, ellagic, and cinnamic acids were identified and quantified, of which ellagic acid was present in the highest quantity (2.36 mg/g dried leaves). By column chromatography and spectral data (1H- and 13C-NMR, IR, and LC-MS) analysis, a compound identified as 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid (1) was purified from the methanolic leaf extract of C. crenata (0.93 mg/g dried leaves). This constituent showed potent inhibition on growth of E. crus-galli, a problematic weed in agricultural practice. The inhibition of the compound 1 (IC50 = 2.62 and 0.41 mM) was >5 fold greater than that of p-hydroxybenzoic acid (IC50 = 15.33 and 2.11 mM) on shoot and root growth of E. crus-galli, respectively. Results suggest that the isolated the compound 1 has potential to develop natural herbicides to manage E. crus-galli. This study is the first to isolate and identify 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid in a plant and report its plant growth inhibitory potential.

The quality of honey is mainly determined by its sensorial, chemical, physical and microbiological properties. The purpose of this research was to evaluate microbiological properties of 72 honey samples and to determine the number and/or presence of aerobic mesophilic and spore-forming bacteria, moulds, yeasts, sulphite-reducing clostridia, bacteria from the Enterobacteriaceae family and Staphylococcus aureus. Microbiological quality of tested samples was considered good and pathogenic bacteria were not present. Inhibitory potential of selected honey samples was also investigated. Among tested honey concentrations (0.1%, 5%, 10%, 25%, 50% and 75%), the final concentration of 75% had the highest potential. Honeydew and chestnut honey exhibited the strongest inhibitory effect against tested bacterial species, while the lowest inhibition was exhibited by linden (lime tree) honey. Comparing the samples of the same honey type, considerably different inhibitory activity can be detected. Overall, the most sensitive bacterium to the inhibitory effect of tested honey samples was S. aureus, while the most resistant one was Enterococcus faecalis. [ABSTRACT FROM AUTHOR]

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• First report of new anthrone-anthraquinone from the stem bark of Rhamnidium elaeocarpum. • Eleocarpanthraquinone (1) exhibited inhibition of the cathepsins B and L. • The most stable conformer was proposed by density functional theory. Chemical investigation of the stem bark of Rhamnidium elaeocarpum resulted in the isolation of eleocarpanthraquinone (1), a new anthrone-anthraquinone linked through a spiroketal bridge and the known anthraquinone chrysophanol (2). The structure of (1) was determined by analysis of spectrometry and spectroscopy data, including HRESIMS, 1D, and 2D NMR experiments, and optical rotation data. Eleocarpanthraquinone (1) was able to inhibit the cysteine proteases cathepsins B and L with an inhibitory potential IC 50 of 3.69 ± 0.38 µM and 1.152 ± 0.025 µM, respectively. Both enzymes showed a parabolic competitive inhibition mechanism and an α parameter with respective values of 0.00253 and 0.0514, implying a positive cooperativity pathway where the binding of the first molecule potentiates the binding of the second molecule. Conformational analysis was performed using density functional theory at the M06-2X/6-31 + G(d,p) level, indicating that the triply H-bonded conformer was the most stable. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the inhibitory effects of benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) against Shiga toxin-producing Escherichia coli (STEC) and enterotoxigenic E. coli (ETEC). Compared with that of PEITC, the antibacterial effect of BITC was more obvious. The minimal inhibitory concentration (MIC) of BITC was 60 and 160 μmol/L for STEC and ETEC, while that of PEITC was 400 μmol/L for both strains. Scanning electron microscopy (SEM) images indicated that treatment with BITC severely affected the cell integrity and led to partly sunken. Incubation of STEC and ETEC with BITC and PEITC for 1 and 4 h decreased total ATP level, while increased extracellular ATP level. Virulence genes were downregulated in dose-dependent fashion upon treatment with subinhibitory concentration of BITC and PEITC, as determined by real-time quantitative polymerase chain reaction (RT-qPCR). The expressions of stx2 , eaeA and ehxA , was significantly lower in STEC treated with 1/4 MIC of PEITC than that of BITC. The inhibitory effects of BITC and PEITC on virulence genes were more obvious in STEC than ETEC. These results suggest that BITC and PEITC affect the strains growth, biological structure and expression of virulence genes of both strains. • Two isothiocyanates had antibacterial effect against two strains of E. coli. • Benzyl isothiocyanate (BITC) was stronger than phenethyl isothiocyanate (PEITC). • BITC disrupted the surface morphology and reduced the total ATP levels in E. coli. • Virulence genes were downregulated by BITC and PEITC in dose-dependent fashion. • Virulence reduction of two ITCs was effective in Shiga toxin-producing E. coli. [ABSTRACT FROM AUTHOR]

Intrinsically disordered proteins (IDPs) play important roles in the regulation of cellular function and in disease, and thus they represent an important group of therapeutic targets. Yet, members of this "disorderome" have not yet been successfully targeted by drugs, primarily because traditional design principles cannot be applied to their highly dynamic, heterogeneous structural states. Binders developed against IDPs so far suffer from very weak binding and inability to act in a cellular context. Here, we describe a possible generic method for the targeting of IDPs via covalent modification, which could entail specific and strong binding and inhibitory potential, making such "warheads" reasonable starting points of drug-development efforts. We demonstrate this principle by addressing the cysteine-specific covalent modification of calpastatin, the IDP inhibitor of the calcium-dependent cysteine protease calpain. We describe the protocol for monitoring the covalent modification of the inhibitor, measuring the K i of its inhibition and comparing it to the K d of its interaction with the enzyme. Our premise is that the underlying principles can be easily adapted to screen for molecules targeting other, disease-related, IDPs in the future.

This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut ( Castanea crenata Sieb. et Zucc), a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli (barnyardgrass), Lactuca sativa (lettuce), and Raphanus sativus (radish). Laboratory and greenhouse trials showed that leaves of C. crenata appeared as a promising material to manage weeds, especially the dicot weeds. By GC-MS and HPLC analyses, gallic, protocatechuic, p -hydroxybenzoic, caffeic, ferulic, ellagic, and cinnamic acids were identified and quantified, of which ellagic acid was present in the highest quantity (2.36 mg/g dried leaves). By column chromatography and spectral data (¹H- and 13 C-NMR, IR, and LC-MS) analysis, a compound identified as 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid ( 1 ) was purified from the methanolic leaf extract of C. crenata (0.93 mg/g dried leaves). This constituent showed potent inhibition on growth of E. crus-galli , a problematic weed in agricultural practice. The inhibition of the compound 1 (IC 50 = 2.62 and 0.41 mM) was >5 fold greater than that of p -hydroxybenzoic acid (IC 50 = 15.33 and 2.11 mM) on shoot and root growth of E. crus-galli , respectively. Results suggest that the isolated the compound 1 has potential to develop natural herbicides to manage E. crus-galli . This study is the first to isolate and identify 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid in a plant and report its plant growth inhibitory potential., Competing Interests: The authors declare no conflict of interest.

Antifungal activity of essential oils (EOs) of Zataria multiflora (thyme) and Syzygium aromaticum (clove) against Aspergillus flavus growth and aflatoxin B 1 production was studied in potato dextrose agar (PDA) and potato dextrose broth (PDB), as well as in Iranian white cheese as a food model. The results showed that the inhibitory potential of EOs in the PDB medium is more than PDA medium. Clove EO on PDB medium prevented fungal growth and aflatoxin B 1 production at 300 and 100 ppm, respectively. However, the thyme EO was not able to inhibit fungal growth completely and showed the strongest inhibition effect at 400 ppm. EOs also had more inhibitory activity in laboratory culture media than the food environments. EOs in all concentrations reduced aflatoxin B 1 production and fungal growth in cheese, but only the clove EO at 150 ppm was able to prevent the fungal growth and aflatoxin B 1 production completely. Thyme EO reduced aflatoxin B 1 value to below detection threshold (2 ppb) at 10 μl. Our findings propose EOs as a natural inhibitor to control fungal contamination of foodstuffs such as Iranian white cheese.