Determination of metal ion content of beverages and estimation of target hazard quotients: a comparative study

Background  

Considerable research has been directed towards the roles of metal ions in nutrition with metal ion toxicity attracting particular attention. The aim of this study is to measure the levels of metal ions found in selected beverages (red wine, stout and apple juice) and to determine their potential detrimental effects via calculation of the Target Hazard Quotients (THQ) for 250 mL daily consumption.     

Design,Synthesis, and In Vitro Anti‐mycobacterial Evaluation 1H‐1,2,3‐triazole‐tethered Ciprofloxacin and Isatin Conjugates

Eight novel 1H‐1,2,3‐triazole‐tethered ciprofloxacin (CPFX) isatin conjugates 5a – h with greater lipophilicity compared with CPFX were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tuberculosis (MTB) H₃₇Rv. The preliminary results showed that all hybrids (MIC: 12.5–100 μg/mL) exhibited considerable activity against M. smegmatis , but less active than the parent CPFX (MIC: 6.25 μg/mL) and the reference INH (MIC: 0.78 μg/mL). Against MTB H₃₇Rv, all hybrids displayed excellent inhibitory activity with MICs ranging from 1.56 to 25 μg/mL, particularly, 5h (MIC: 1.56 μg/mL) was twofold more active CPFX (MIC: 3.12 μg/mL), warrant further investigations.     

Design,Synthesis, and Biological and In Silico Study of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

A novel series of fluorine‐containing quinoline hybrid thiosemicarbazide analogues ( 8a–8l ) were synthesized and tested for their biological activities. The antibacterial results demonstrated that compounds 8d and 8l [minimal inhibitory concentration (MIC) 62.5 μg/mL] were shown to have higher biological activity than ampicillin against Escherichia coli. Compound 8b (MIC 25 μg/mL) was shown to have the highest activity than was ampicillin against Staphylococcus aureus. The antifungal results demonstrated that compound 8j (MIC 100 μg/mL) has shown good activity. Most of the targeted compounds have shown potent antimalarial activity. Compounds 8d (0.19 μg/mL), 8g (0.30 μg/mL), 8h (0.36 μg/mL), 8k (0.10 μg/mL), 8l (0.28 μg/mL), 8k (0.10 μg/mL), and 8l (0.28 μg/mL) have notable activity than does the reference drug quinine. Compounds 8d (0.27 μg/mL), 8g (0.30 μg/mL), and 8k (0.17 μg/mL) have shown excellent activity against chloroquine‐resistant strain. The MTT assay performed on peripheral blood lymphocyte cultures showed a high percentage of lymphocyte viability [ 8d (99.64), 8g (99.46), 8h (98.83), and 8k (99.51)] at a maximum dose (10 μg/mL), depicting no cytotoxicity of these compounds on human lymphocytes in vitro. A molecular docking study was performed on Pf‐DHFR‐TS inhibitor. A molecular dynamics study has shown compound 8g to have better affinity with protein. ADME‐Tox and pharmacophore study of synthesized compounds suggested prediction of active site.     

Microwave-assisted and scandium triflate catalyzed synthesis of tetrahydrobenzo[<Emphasis Type="Italic">a</Emphasis>]xanthen-11-ones

Abstract  

Synthesis of 12-aryl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-ones was achieved by one-pot condensation of β-naphthol, substituted benzaldehydes, and 1,3-dicarbonyl compounds catalyzed by Sc(OTf)₃ under microwave irradiation in excellent isolated yields. The catalyst was recycled up to four cycles with no appreciable loss in catalytic activity. The compounds were evaluated for Src kinase activity and anticancer activity.     

Synthesis of Novel 1,2,4‐Triazole‐3‐thione Derivatives as Influenza Neuraminidase Inhibitors

A series of 1,2,4‐triazole‐3‐thione derivatives ( 6a – 6t ) were synthesized and evaluated against influenza viruses (H1N1) neuraminidase (NA) in vitro. Eighteen compounds exhibited inhibitory potency with IC₅₀ values ranging from 14.68 ± 0.49 to 39.85 ± 4.23 μg/mL. Among them, compounds 6e and 6h showed significant inhibitory activity with IC₅₀ values of 14.97 ± 0.70 and 14.68 ± 0.49 μg/mL, respectively. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction between active compounds and NA.     

Synthesis,Biological Evaluation,and Molecular Docking Studies of Some N‐thiazolyl Hydrazones and Indenopyrazolones

Two new series of N‐thiazolyl hydrazones ( 3a – h ) and indenopyrazolones ( 4a – h ) were synthesized by the reaction of various 2‐acyl‐(1H)‐indene‐1,3(2H)‐diones, thiosemicarbazide, and phenacyl bromide/substituted phenacyl bromides. The in vitro antimicrobial activity of these synthesized compounds was assayed against four bacteria, namely, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, and two fungi, namely, Candida albicans and Aspergillus niger, by employing serial dilution method. Ciprofloxacin and fluconazole were used as antibacterial and antifungal reference drugs, respectively. Results of antimicrobial assay showed that the tested compounds have broad range of activity. The compounds 3h and 4a against C. albicans displayed more potency than fluconazole whereas 3b and 3c against B. subtilis showed activity comparable with ciprofloxacin. The synthesized indenopyrazolones ( 4a – h ) were evaluated for their in vitro antioxidant activity by 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging assay using ascorbic acid as reference. Compound 4b exhibited the highest 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging with IC₅₀ value 33.14 μg/mL. The observed results of antimicrobial activity were supported by molecular docking study performed to understand the binding interaction of hydrazones ( 3a – h ) and indenopyrazolones ( 4a – h ) with lanosterol 14α‐demethylase.     

Myosin-cross-reactive antigen (MCRA) protein from <Emphasis Type="Italic">Bifidobacterium breve</Emphasis> is a FAD-dependent fatty acid hydratase which has a function in stress protection

Background  

The aim of this study was to determine the catalytic activity and physiological role of myosin-cross-reactive antigen (MCRA) from Bifidobacterium breve NCIMB 702258. MCRA from B. breve NCIMB 702258 was cloned, sequenced and expressed in heterologous hosts (Lactococcus and Corynebacterium) and the recombinant proteins assessed for enzymatic activity against fatty acid substrates.     

Synthesis and characterization of a poly(p‐phenylenediamine)‐based electrospun nanofiber for the micro‐solid‐phase extraction of organophosphorus pesticides from drinking water and lemon and orange juice samples

A new micro‐solid‐phase extraction sorbent was synthesized by electrospinning poly(p‐phenylenediamine)/poly(vinyl alcohol) in the presence of cetyltrimethylammonium bromide. The modified nanofiber was prepared by removing the majority of the poly(vinyl alcohol) from the nanofiber blend by exposing it to the hot water. Scanning electron microscopy and surface analysis were performed to study the homogeneity and porosity of the electrospun nanofiber. In addition, Fourier transform infrared spectroscopy was applied for more characterization. The capability of the new nanofiber was explored by applying it in the extraction and preconcentration of organophosphorus pesticides from aqueous medium. After solvent desorption, the extracted analytes were analyzed by high‐performance liquid chromatography with diode array detection. Under the optimum conditions, the relative standard deviation values at the concentration level of 50 ng/mL were in the range of 4.8–8.3%. The calibration curve showed linearity in the range of 0.5–500 ng/mL, and the limits of detection (S/N = 3) for the studied compounds were 0.15 ng/mL. By analyzing Tehran drinking water, lemon juice, sour lemon juice, orange juice and sour orange juice, the applicability of the presented method was investigated and the relative recoveries were in the range of 76–102%.     

Studies on the synthesis, characterization, binding with DNA and activities of two cis-planaramineplatinum(II) complexes of the form: cis-PtL(NH3)Cl2 where L = 3-hydroxypyridine and 2,3-diaminopyridine

Background  

Cis-planaramineplatinum(II) complexes like their trans isomers are often found to be active against cancer cell lines. The present study deals with the synthesis, characterization and determination of activity of new cis-planaramineplatinum(II) complexes.     

Synthesis of novel 2,3‐disubstituted quinazolin‐4(3H)‐one derivatives containing hydrazone skeleton as potent urease inhibitors and their antimicrobial activities

A new series of quinazolinones containing hydrazone moiety were synthesized, and their inhibitory activities on urease were assessed in vitro. Most of the compounds exhibited potent urease inhibitory activity. Among the synthesized compounds, molecule 4a bearing furan ring has the best inhibitory effect against urease with IC₅₀ = 2.90 ± 0.11 μg/mL. Compounds 4f , 4g , 4h , 4i , and 4j have hydroxy group on phenyl ring. Compound 4i is the most active inhibitor among these compounds with IC₅₀ = 5.01 ± 0.10 μg/mL, which has 3‐Cl and 4‐Br on phenyl ring. Also, newly synthesized compounds had been tested for their antimicrobial effects against three of Gram‐positive bacteria (Bacillus cereus 702 Roma, Staphylococcus aureus ATCC 25923, and Streptococcus pyogenes ATCC 19615) and three of Gram‐negative bacteria (Escherichia coli ATCC 25922, Proteus vulgaris ATCC 13315, and Pseudomonas aeruginosa ATCC 27853). Antimicrobial activity results show that compounds 4a , 4h , 4j , 4f , and 4l have the lowest minimum inhibitory concentration (MIC) value of 1000 μg/mL to all tested bacteria. The other compounds have the MIC value of >1000 μg/mL to all tested bacteria.     

Orthophosphate binding at the dimer interface of <Emphasis Type="Italic">Corynebacterium callunae</Emphasis> starch phosphorylase: mutational analysis of its role for activity and stability of the enzyme

Background  

Orthophosphate recognition at allosteric binding sites is a key feature for the regulation of enzyme activity in mammalian glycogen phosphorylases. Protein residues co-ordinating orthophosphate in three binding sites distributed across the dimer interface of a non-regulated bacterial starch phosphorylase (from Corynebacterium callunae) were individually replaced by Ala to interrogate their unknown function for activity and stability of this enzyme.     

Synthesis and antiproliferative activity of multisubstituted N-fused heterocycles against the Hep-G2 cancer cell line

Abstract  

Pyrrolo[1,2-a]imidazole and pyrrolo[2,1-b]thiazole derivatives were synthesized in a one-pot procedure by [3 + 2] cycloaddition reactions of the corresponding imidazolium ylides and thiazolium ylides with an alkene followed by oxidative aromatization of the primary cycloadducts under the action of the mild oxidant tetrakispyridinecobalt(II) dichromate. Antiproliferative activity of 14 new bicyclic N-fused heterocycles against the human hepatocellular liver carcinoma (Hep-G2) cell line were examined by the MTT method. Some of the compounds showed favorable antiproliferative activity, especially compound 3i displayed potent antiproliferative activities with an IC₅₀ value of 0.36 μg/cm³.     

Molecular cloning,gene structure and expression profile of two mouse peroxisomal 3-ketoacyl-CoA thiolase genes

Background  

In rats, two peroxisomal 3-ketoacyl-CoA thiolase genes (A and B) have been cloned, whereas only one thiolase gene is found in humans. The aim of this study was thus to clone the different mouse thiolase genes in order to study both their tissue expression and their associated enzymatic activity.     

Synthesis, chemical properties, and antimicrobial activity of 2- and 2,3-substituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones

Abstract  

Mono- and disubstituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones were synthesized by the reaction of dihydro-1-(3-hydroxy- and 4-hydroxyphenyl)pyrimidine-2,4(1H,3H)-diones and their 5- and 6-methyl derivatives with 2,3-dichloro-1,4-naphthoquinone. Their stability in alkaline and acidic media was investigated. Four of the compounds exhibited good antimicrobial activity against Staphylococcus aureus, Mycobacterium luteum, Candida tenuis, and Aspergillus niger.     

Ciprofloxacin‐isatin‐1H‐1,2,3‐triazole Hybrids: Design,Synthesis, and in vitro Anti‐tubercular Activity against M. tuberculosis

A new set of ciprofloxacin (CPFX)‐isatin‐1H‐1,2,3‐triazole hybrids 6a – l with greater lipophilicity compared with the parent CPFX was designed, synthesized, and assessed for their in vitro anti‐mycobacterial activity against Mycobacterium tuberculosis (MTB) H₃₇Rv as well as cytotoxicity in VERO cell line. The preliminary results showed that all hybrids (MIC: 0.39–50 μg/mL) exhibited promising activities against MTB H₃₇Rv, and six of them (MIC: 0.39–1.56 μg/mL) were more active than the parent CPFX (MIC: 3.12 μg/mL). In particular, the most active conjugate 6h (MIC: 0.39 μg/mL) was comparable with RIF (MIC: 0.39 μg/mL), and eight times more potent than CPFX. All conjugates (CC₅₀: 4–64 μg/mL) were more toxic than the parent (CC₅₀: 128 μg/mL) in VERO cell lines, and the most active hybrids, which also displayed the highest cytotoxicity, should be further optimized.     

Isatin‐(thio)semicarbazide/oxime‐1H‐1,2,3‐triazole‐coumarin Hybrids: Design,Synthesis, and in vitro Anti‐mycobacterial Evaluation

Isatin and coumarin derivatives with potential anti‐tubercular activity, while (thio)semicarbazide/oxime and 1H‐1,2,3‐triazole moieties exhibited favorable properties such as hydrogen bonding and/or metal chelation capability, so integration of the four pharmacophores into one molecule may provide more effective anti‐tubercular candidates. Based on the consideration earlier, 12 isatin‐(thio)semicarbazide/oxime‐1H‐1,2,3‐triazole‐coumarin hybrids 8a–l were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against M. tuberculosis (MTB) H₃₇Rv and MDR‐TB. The results showed that all the hybrids (MIC: 50–>200 μg/mL) exhibited weak to moderate inhibitory activity against MTB H₃₇Rv and MDR‐TB, which were far less potent than the references isoniazid (MIC: 0.05 μg/mL) and rifampicin (MIC: 0.39 μg/mL) against MTB H₃₇Rv. The most active hybrid 8h (MIC: 50 μg/mL) was comparable with rifampicin (MIC: 32 μg/mL) and more active than isoniazid (MIC: >128 μg/mL) against MDR‐TB, could be act as a lead for further optimization. Moreover, the enriched structure–activity relationship paved the way to the further rational development of this kind of hybrids.     

Synthesis,Docking, and Pharmacological Evaluation of Derivatives of α‐Aminoketones Appended to Sydnones as Potent Antitubercular and Antifungal Scaffolds

3‐Arylsydnones are reported to possess striking pharmaceutical potency. α‐Aminoketone, a biologically active structural unit, is built at the fourth (electrophilic) position of sydnone and further derivatized with secondary amine and tetrazoles. The α‐aminoketone derivatives of sydnones coupled with secondary amines 4a – n were docked on enoyl acyl carrier protein (ACP) reductase from Mycobacterium tuberculosis, which revealed that compounds 4b , 4f , and 4i showed efficient C score values with different binding modes and hydrogen bonding. Further, these compounds were screened for antimycobacterial activity; among them, compound 4f displayed sensitivity at 6.25 μg/mL compared with the standard drug (Streptomycin) against M. tuberculosis (H₃₇R_V strain). In addition to this, α‐aminoketone derivatives of sydnones coupled with tetrazoles 8a – h were evaluated for antifungal activity. In the antifungal activity, compound 8b has exhibited potent activity at 6.25 μg/mL against Candida albicans and compound 8g at 0.4 μg/mL against Aspergillus fumigatus. The antifungal activities are comparatively better than standard antifungal agent Fluconazole at these drug concentrations. Alongside characterization of the final compounds by Fourier transform infrared, mass, ¹H NMR, and ¹³C NMR spectral analyses, compounds 8b and 8g were confirmed by X‐ray crystallographic studies.     

The yeast <Emphasis Type="Italic">ISN1</Emphasis> (<Emphasis Type="Italic">YOR155c</Emphasis>) gene encodes a new type of IMP-specific 5'-nucleotidase

Background  

The purine salvage enzyme inosine 5'-monophosphate (IMP)-specific 5'-nucleotidase catalyzes degradation of IMP to inosine. Although this enzymatic activity has been purified and characterized in Saccharomyces cerevisiae, the gene encoding IMP 5'-nucleotidase had not been identified.     

Efficient Synthesis of Novel 3‐Phenyl‐5‐thioxo‐3,4,5,6‐tetrahydroimidazo[4,5‐c]pyrazole‐2(1H)‐carbothioamide Derivatives Using a CeO2–MgO Catalyst and Evaluation of Antimicrobial Activity

Imidazo[4,5‐c ]pyrazole derivatives ( 3a–f , 4a–f , and 5a–f ) were efficiently synthesized by one‐pot three‐component reactions using CeO₂–MgO as the catalyst. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopic analyses. The in vitro antimicrobial activity of the synthesized compounds against various bacterial and fungal strains was screened. Compound 3b was highly active [minimum inhibitory concentration (MIC): 0.5 μg/mL] against Gram‐positive Staphylococcus aureus , and compounds 3b , 3f , 4d , and 4e were highly active (MIC: 0.5, 2, 2, and 0.5 μg/mL, respectively) against Gram‐negative Pseudomonas aeruginosa and Klebsiella pneumoniae , relative to standard ciprofloxacin in the antibacterial activity screening. Compounds 3b and 4f were highly active (MIC: 4 and 0.5 μg/mL, respectively) against Aspergillus fumigatus and Microsporum audouinii in the antifungal activity screening compared with the clotrimazole standard.     

Determination of thermodynamic parameters of Xerocomus chrysenteron lectin interactions with N-acetylgalactosamine and Thomsen-Friedenreich antigen by isothermal titration calorimetry

Background  

Lectins are carbohydrate-binding proteins which potentially bind to cell surface glycoconjugates. They are found in various organisms including fungi. A lectin from the mushroom Xerocomus chrysenteron (XCL) has been isolated recently. It shows insecticidal activity and has antiproliferative properties.