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The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl βeta-cyclodextrin (HPβ-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer-Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.

Lignocellulose, the structural component of plant cells, is a major agricultural byproduct and the most abundant terrestrial source of biopolymers on Earth. The complex and insoluble nature of lignocellulose limits its conversion into value-added commodities, and currently, efficient transformation requires expensive pretreatments and high loadings of enzymes. Here, we report on a fungus from the Parascedosporium genus, isolated from a wheat-straw composting community, that secretes a large and diverse array of carbohydrate-active enzymes (CAZymes) when grown on lignocellulosic substrates. We describe an oxidase activity that cleaves the major β-ether units in lignin, thereby releasing the flavonoid tricin from monocot lignin and enhancing the digestion of lignocellulose by polysaccharidase mixtures. We show that the enzyme, which holds potential for the biorefining industry, is widely distributed among lignocellulose-degrading fungi from the Sordariomycetes phylum.

In the present study, a novel series of polyfunctionalized imidazopyrimidines 6a-u and 9a-d were efficiently constructed by a domino reaction between 2-imino-6-substituted-2,3-dihydropyrimidin-4(1H)-ones 4a-d or 8a-c and 2-bromoacetophenones 5a-i under mild basic conditions. The synthesized series were screened for their antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive (+) bacteria, as well as against Gram-negative (-) bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhi. Most of the synthesized derivatives of imidazopyrimidines 6 and 9 showed remarkable selectivity against Gram(-) bacteria over the Gram(+) ones. Compounds 6c, 6f, and 6g displayed potent and broad-spectrum antibacterial activity against all tested strains. Compounds 6f and 6g displayed promising inhibitory activity on GryB ATPase from E. coli with IC50 = 1.14 and 0.73 μM, respectively. Simultaneously, some of the synthesized imidazopyrimidines were screened for their antiproliferative activity against 60 cancer cell lines at a concentration of 10 μM. Compound 9d showed potent activity against most of the tested cell lines, with a mean growth inhibition of 37%. The ADME (absorption, distribution, metabolism, and excretion) prediction study demonstrated that the synthesized hits have, in addition to their promising chemotherapeutic activity, acceptable pharmacokinetic properties, and a drug-likeness nature to be further developed.

The potential application for the multiparticulate synbiotic microcapsule in yoghurt production was presented in the current study. Initially, three different formulae were fabricated to investigate the mechanism of action. This was followed by characterization the size of both of the nanoparticles and the final multiparticulate microcapsule. The yoghurt was then formed and the formulae were added and subjected to 4 weeks storage period. The viability of Bifidobacterium mixed cultures was monitored weekly. The results showed the viability of Bifidobacterium cultures was enhanced when double coated microcapsule was applied compared to the free one. The enhancement was further boosted when inulin was incorporated in either free form or in the form of nanoparticles. Scanning electron microscope image showed the final multiparticulate microcapsule has size of 700 μm while the laser diffraction particle size analyzer revealed the nanoparticles size is 118.1±4 nm. It was concluded that both of the double coat layer covering the multiparticulate microcapsule and the entrapped inulin, significantly enhanced the survivability of the encapsulated Bifidobacterium cultures in yoghurt during the shelf period.

A novel synbiotic multiparticulate microparticle was produced in the current study to expand the synbiotic industrial applications. Initially, the inulin was fabricated into PLGA nanoparticles. After the inulin entrapment efficiency was boosted to reach 92.9 ± 8.4% by adjusting the formulation parameters, the developed particles were characterized by different techniques such as particle size analyzer, TEM, and TLC. The obtained data showed that the particle size was 115.8 ± 82.7 nm, the particles had smooth surface and round shape, and the fabrication procedure did not affect the integrity of the inulin. Later, the inulin loaded nanoparticles together with selected Bifidobacterium species were double coated with gum arabic and alginate. The maximum survivability of the encapsulated Bifidobacterium in the simulated gastric solution reached 88.29% of the initial population, which was significantly higher than the survivability of the free bacteria. Finally, the inulin release from the multiparticulate microparticles was studied and found to be sustained over three days.

A series of directed knockout experiments, combined with an in vitro assay of pathway components, has elucidated for the first time the chemical steps involved in the biosynthesis of the tropolone class of fungal maleic anhydrides. The pathway involves the stepwise oxidation of aldehyde and methyl carbon atoms to form a 1,2-dicarboxylate. A hydrolase-catalyzed interconversion of this and the corresponding maleic anhydride, followed by decarboxylation of the diacid leads to the pathway's final product of stipitatic acid.

An FAD-dependent monooxygenase encoding gene (SorbC) was cloned from Penicillium chrysogenum E01-10/3 and expressed as a soluble protein in Escherichia coli. The enzyme efficiently performed the oxidative dearomatisation of sorbicillin and dihydrosorbicillin to give sorbicillinol and dihydrosorbicillinol respectively. Bioinformatic examination of the gene cluster surrounding SorbC indicated the presence of two polyketide synthase (PKS) encoding genes designated sorbA and sorbB. The gene sorbA-encodes a highly reducing iterative PKS while SorbB encodes a non-reducing iterative PKS which features a reductive release domain usually involved in the production of polyketide aldehydes. Using these observations and previously reported results from isotopic feeding experiments a new and simpler biosynthetic route to the sorbicillin class of secondary metabolites is proposed which is consistent with all reported experimental results.