Synthesis,antiproliferative and antibacterial activity of new amides of salinomycin

A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE).     

The synthesis and biological evaluation of alkyl and benzyl naphthyridinium analogs of eupolauridine as potential antimicrobial and cytotoxic agents

Eupolauridine, an indenonaphthyridine alkaloid, has been previously reported by us to exhibit antifungal activity. This study describes the synthesis of new alkyl and benzyl naphthyridinium/pyridinium analogs of eupolauridine as potential antifungal agents. A majority of the analogs exhibited antifungal activity against opportunistic pathogens such as Candida albicans and Cryptococcus neoformans. Several of them were also effective against bacteria (Staphylococcus aureus, MRS, Pseudomonas and Mycobacterium) and the malaria parasite (Plasmodium falciparum) to variable extents. A number of analogs were also cytotoxic to human cancer cell lines.     

Inhibitors for the bacterial ectonucleotidase Lp1NTPDase from Legionella pneumophila

Legionella pneumophila is an aerobic, Gram-negative bacterium of the genus Legionella, which constitutes the major causative agent of Legionnaires’ disease. Recently a nucleoside triphosphate diphosphohydrolase (NTPDase) from L. pneumophila was identified and termed Lp1NTPDase; it was found to be a structural and functional homolog of mammalian NTPDases catalyzing the hydrolysis of ATP to ADP and ADP to AMP. Its activity is believed to contribute to the virulence of Legionella pneumophila. Therefore Lp1NTPDase inhibitors are considered as novel antibacterial drugs. However, only weakly potent compounds are available so far. In the present study, a capillary electrophoresis (CE)-based enzyme assay for monitoring the Lp1NTPDase activity was established. The enzymatic reaction was performed in a test tube followed by separation of substrate and products by CE and subsequent quantification by UV analysis. After kinetic characterization of the enzyme, a series of 1-amino-4-ar(alk)ylamino-2-sulfoanthraquinone derivatives structurally related to the anthraquinone dye Reactive Blue 2, a non-selective ecto-NTPDase inhibitor, was investigated for inhibitory activity on Lp1NTPDase using the CE-based enzyme assay. Derivatives bearing a large lipophilic substituent (e.g., fused aromatic rings) in the 4-position of the 1-amino-2-sulfoanthraquinone showed the highest inhibitory activity. Compounds with IC₅₀ values in the low micromolar range were identified. The most potent inhibitor was 1-amino-4-[phenanthrene-9-yl-amino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (28, PSB-16131), with an IC₅₀-value of 4.24 μM. It represents the most potent Lp1NTPDase inhibitor described to date. These findings may serve as a starting point for further optimization. Lp1NTPDase inhibition provides a novel approach for the (immuno)therapy of Legionella infections.     

Emerging role of ferrous iron in bacterial growth and host–pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy

Chemical tools capable of detecting ferrous iron with oxidation-state specificity have only recently become available. Coincident with this development in chemical biology has been increased study and appreciation for the importance of ferrous iron during infection and more generally in host–pathogen interaction. Some of the recent findings are surprising and challenge long-standing assumptions about bacterial iron homeostasis and the innate immune response to infection. Here, we review these recent developments and their implications for antibacterial therapy.     

Antibacterial activity of disodium succinoyl glycyrrhetinate,a derivative of glycyrrhetinic acid against Streptococcus mutans

Streptococcus mutans is a cariogenic bacterium that localizes in the oral cavity. Glycyrrhetinic acid (GRA) is a major component of licorice extract. GRA and several derivatives, including disodium succinoyl glycyrrhetinate (GR‐SU), are known to have anti‐inflammatory effects in humans. In this study, the antimicrobial effect of GRA and its derivatives against the S. mutans UA159 strain were investigated. Minimum inhibitory concentrations (MICs) of GRA and GR‐SU showed antibacterial activity against the S. mutans strain, whereas other tested derivatives did not. Because GR‐SU is more soluble than GRA, GR‐SU was used for further experiments. The antibacterial activity of GR‐SU against 100 S. mutans strains was evaluated and it was found that all strains are susceptible to GR‐SU, with MIC values below 256 µg/mL. A cell viability assay showed that GR‐SU has a bacteriostatic effect on S. mutans cells. As to growth kinetics, sub‐MICs of GR‐SU inhibited growth. The effect of GR‐SU on S. mutans virulence was then investigated. GR‐SU at sub‐MICs suppresses biofilm formation. Additionally, GR‐SU greatly suppresses the pH drop caused by the addition of glucose and glucose‐induced expression of the genes responsible for acid production (ldh and pykF) and tolerance (aguD and atpD). Additionally, expression of enolase, which is responsible for the carbohydrate phosphotransferase system, was not increased in the presence of GR‐SU, indicating that GR‐SU suppresses incorporation of sugars into S. mutans. In conclusion, GR‐SU has antibacterial activity against S. mutans and also decreases S. mutans virulence.     

Antibacterial activity of Turkish propolis and its qualitative and quantitative chemical composition

The antibacterial activity of propolis from different regions of Turkey was studied, accompanied by TLC and GC-MS analyses of its chemical composition and spectrophotometric quantification of the most important active principles. All six samples were active against the bacterial test strains used; however, samples 1 (Yozgat), 2 (Izmir) and 3 (Kayseri) were more active than samples 4 (Adana), 5 (Erzurum) and 6 (Artvin). By TLC comparison all samples were found to contain poplar taxonomic markers but in samples 4 (Adana), 5 (Erzurum) and 6 (Artvin), different substances were observed, which were not present in P. nigra L. bud exudate. The typical poplar samples 1 (Yozgat), 2 (Izmir) and 3 (Kayseri) displayed very similar phenolic and flavonoid content. Samples 4 (Adana), 5 (Erzurum) and 6 (Artvin) were characterized by low phenolic and very low flavonoid concentrations. Qualitative analysis by GC-MS revealed that sample 4 (Adana) contained diterpenic acids and high percent of cinnamyl cinnamate, sample 5 (Erzurum)-significant amounts of hydroxy fatty acids and triterpenic alcohoLs, and sample 6 (Artvin)-phenolic glycerides, characteristic for the bud exudate of Populus euphratica Oliv. The results confirm the importance of phenolics for propolis antibacterial activity, and the significance of P. nigra L. as a propolis source, which provides the hive with the best defense against microorganisms.     

Development and evaluation of different strategies for the clean synthesis of silver nanoparticles using Yarrowia lipolytica and their antibacterial activity

An environment-friendly, cheap method, biogenic synthesis of silver nanoparticles (AgNPs) is interesting as compared to physical and chemical synthesis methods. The aim of the present study was to utilize the inherent capability of Yarrowia lipolytica as a novel biocatalyst for green production of AgNPs using different strategies, including growing cells, resting cells, and cell-free extracts (CFE) under optimized reaction conditions. The produced AgNPs were evaluated with UV–vis spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray analysis, X-ray diffraction, and Fourier transform infrared spectrometry. In the growing cells strategy, Y. lipolytica produced spherical AgNPs under the optimized conditions, 2.5 mM of silver ions, 7.5 g/l of yeast biomass, a temperature of 30 °C, a pH of 6, and a shaking rate of 50 rpm after 48 h. The sizes and monodispersity of the AgNPs in the resting cells strategy were better than those in the other two. However, the AgNPs were produced faster in the CFE strategy. The antibacterial activity and minimal inhibitory concentration of the AgNPs against certain Gram-positive and Gram-negative bacteria were determined by the agar well diffusion and broth microdilution methods. The AgNPs had a considerable antibacterial effect compared to chloramphenicol as a broad-spectrum antibiotic.     

New prenylated dihydrochalcones from the leaves of Artocarpus elasticus

The leaves of Artocarpus elasticus collected in Thailand were investigated for chemical constituents. Four new prenylated dihydrochalcones named elastichalcones C, D, E, F (1, 3, 5, 6) together with elastichalcone B (2) and artocarpanone (4) were isolated. Their structures were determined from analysis of spectroscopic data. Elastichalcone C (1) exhibited good antibacterial activity and cytotoxicity.     

Preparation of 8-hydroxyquinoline derivatives as potential antibiotics against Staphylococcus aureus

This work describes the preparation of quinoline compounds as possible anti-bacterial agents. The synthesized quinoline derivatives show anti-bacterial activity towards Staphylococcus aureus. It is interesting to observe that the synthetic 5,7-dibromo-2-methylquinolin-8-ol (4) shows a similar minimum inhibitory concentration of 6.25 μg/mL as compared to that of methicillin (3.125 μg/mL) against Staphylococcus aureus.