Mohamed Mehiri

Pan-genotypic Hepatitis C Virus Inhibition by Natural Products Derived from the Wild Egyptian Artichoke.

ABSTRACT Hepatitis C virus (HCV) infection is the leading cause of chronic liver diseases. Water extracts of the leaves of the wild Egyptian artichoke (WEA) [Cynara cardunculus L. var. sylvestris (Lam.) Fiori] have been used for centuries in the Sinai Peninsula to treat hepatitis symptoms. Here we isolated and characterized six compounds from the water extracts of WEA and evaluated their HCV inhibition capacities in vitro. Importantly, two of these compounds, grosheimol and cynaropicrin, inhibited HCV with half-maximal effective concentrations (EC50s) in the low micromolar range. They inhibited HCV entry into target cells and were active against both cell-free infection as well as cell-cell transmission. Furthermore, the antiviral activity of both compounds was pan-genotypic as HCV genotypes 1a, 1b, 2b, 3a, 4a, 5a, 6a, and 7a were inhibited. Thus, grosheimol and cynaropicrin are promising candidates for the development of new pan-genotypic entry inhibitors of HCV infection. IMPORTANCE Because there is no preventive HCV vaccine available today, the discovery of novel anti-HCV cell entry inhibitors could help develop preventive measures against infection. The present study describes two compounds isolated from the wild Egyptian artichoke (WEA) with respect to their structural elucidation, absolute configuration, and quantitative determination. Importantly, both compounds inhibited HCV infection in vitro. The first compound was an unknown molecule, and it was designated “grosheimol,” while the second compound is the known molecule cynaropicrin. Both compounds belong to the group of sesquiterpene lactones. The mode of action of these compounds occurred during the early steps of the HCV life cycle, including cell-free and cell-cell infection inhibition. These natural compounds present promising candidates for further development into anti-HCV therapeutics.

Differential distribution of lipids in epidermis, gastrodermis and hosted Symbiodinium in the sea anemone Anemonia viridis

Cnidarian-dinoflagellate symbiosis mainly relies on nutrient recycling, thus providing both partners with a competitive advantage in nutrient-poor waters. Essential processes related to lipid metabolism can be influenced by various factors, including hyperthermal stress. This can affect the lipid content and distribution in both partners, while contributing to symbiosis disruption and bleaching. In order to gain further insight into the role and distribution of lipids in the cnidarian metabolism, we investigated the lipid composition of the sea anemone Anemonia viridis and its photosynthetic dinoflagellate endosymbionts (Symbiodinium). We compared the lipid content and fatty acid profiles of the host cellular layers, non-symbiotic epidermal and symbiont-containing gastrodermal cells, and those of Symbiodinium, in a mass spectrometry-based assessment. Lipids were more concentrated in Symbiodinium cells, and the lipid class distribution was dominated by polar lipids in all tissues. The fatty acid distribution between host cell layers and Symbiodinium cells suggested potential lipid transfers between the partners. The lipid composition and distribution was modified during short-term hyperthermal stress, mainly in Symbiodinium cells and gastrodermis. Exposure to elevated temperature rapidly caused a decrease in polar lipid C18 unsaturated fatty acids and a strong and rapid decrease in the abundance of polar lipid fatty acids relative to sterols. These lipid indicators could therefore be used as sensitive biomarkers to assess the physiology of symbiotic cnidarians, especially the effect of thermal stress at the onset of cnidarian bleaching. Overall, the findings of this study provide some insight on key lipids that may regulate maintenance of the symbiotic interaction.

Unusual Nitrogenous Phenalenone Derivatives from the Marine-Derived Fungus Coniothyrium cereale

The new phenalenone metabolites 1, 2, 4, and 6 were isolated from the marine-derived endophytic fungus Coniothyrium cereale, in addition to the ergostane-type sterol (3) and entatrovenetinone (5). Compounds 1 and 2 represent two unusual nitrogen-containing compounds, which are composed of a sterol portion condensed via two bonds to phenalenone derivatives. Compound 6, which contains unprecedented imine functionality between two carbonyl groups to form a oxepane -imine-dione ring, exhibited a moderate cytotoxicity against K562, U266, and SKM1 cancer cell lines. Moreover, molecular docking studies were done on estrogen receptor α-ligand binding domain (ERα-LBD) to compounds 1 and 2 to correlate with binding energies and affinities calculated from molecular docking to the anti-proliferative activity.

Carboxythiazole is a key microbial nutrient currency and critical component of thiamin biosynthesis

Almost all cells require thiamin, vitamin B1 (B1), which is synthesized via the coupling of thiazole and pyrimidine precursors. Here we demonstrate that 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole-2-carboxylic acid (cHET) is a useful in vivo B1 precursor for representatives of ubiquitous marine picoeukaryotic phytoplankton and Escherichia coli – drawing attention to cHET as a valuable exogenous micronutrient for microorganisms with ecological, industrial, and biomedical value. Comparative utilization experiments with the terrestrial plant Arabidopsis thaliana revealed that it can also use exogenous cHET, but notably, picoeukaryotic marine phytoplankton and E. coli were adapted to grow on low (picomolar) concentrations of exogenous cHET. Our results call for the modification of the conventional B1 biosynthesis model to incorporate cHET as a key precursor for B1 biosynthesis in two domains of life, and for consideration of cHET as a microbial micronutrient currency modulating marine primary productivity and community interactions in human gut-hosted microbiomes.

The (+)-cis- and (+)-trans-Olibanic Acids: Key Odorants of Frankincense

Frankincense (olibanum) is one of the oldest aromatic materials used by humans, but the key molecular constituents contributing to its characteristic odor remained unknown. Reported herein is the discovery that (1S,2S)-(+)-trans- and (1S,2R)-(+)-cis-2-octylcyclopropyl-1-carboxylic acids are highly potent and substantive odorants occurring in ppm amounts in all of the frankincense samples analyzed, even those showing radically different volatile compositions. These cyclopropyl-derived acids provide the very characteristic old churchlike endnote of the frankincense odor.

Author Correction: Carboxythiazole is a key microbial nutrient currency and critical component of thiamin biosynthesis

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

New bioactive chlorinated cyclopentene derivatives from the marine-derived Fungus Phoma sp

AbstractThe new halogenated metabolites cryptophomic acid (1), cryptodiol (2), and cryptotriol (3) and the known dihydro-isocoumarin derivative 4, were isolated from the marine-derived fungus Phoma sp.135. The structural elucidation of these compounds was achieved by extensive analysis of spectroscopic data including 1D- and 2D-NMR, HRMS, optical rotation, UV, and IR. The absolute configuration of cryptophomic acid (1) was determined by using circular dichroism and TD-DFT ECD calculations of the solution conformers. The relative configurations of cryptodiol (2) and cryptotriol (3) were elucidated by a detailed analysis of the spectroscopic data and quantum mechanical calculation of NMR chemical shifts, based also on the newly reported +u2009approach. The dihydro-isocoumarin derivative 4 was also produced by the same fungus and its structure was established as (R)-8-hydroxy-6-methoxy-3-methy-3,4-dihydro-isocoumarin (4), often referred to 6-methoxymellein and its chemical structure and absolute configuration were further confirmed through X-ray diffraction analysis. We report here the new compounds 1–3 and the crystallographic data of compound 4 for the first time. Additionally, we report significant antimicrobial activity of compounds 1–3 against Escherichia coli, Bacillus subtilis, Mycobacterium phlei, and Staphylococcus aureus and they showed no lethality against brine shrimp.n