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Dermacozines, A New Phenazine Family from Deep-Sea Dermacocci Isolated from a Mariana Trench Sediment

Research Abstract
Dermacoccus abyssi sp. nov., strains MT1.1 and MT1.2 are actinomycetes isolated from Mariana Trench sediment at a depth of 10 898 m. Fermentation using ISP2 and 410 media, respectively, lead to production of seven new oxidized and reduced phenazine-type pigments, dermacozines A–G (1–7), together with the known phenazine-1-carboxylic acid (8) and phenazine-1,6-dicarboxylic acid (9). Extensive use was made of 1D and 2D-NMR data, and high resolution MS to determine the structures of the compounds. To confirm the structure of the most complex pentacyclic analogue (5) we made use of electronic structure calculations to compare experimental and theoretical UV-Vis spectra, which confirmed a novel structural class of phenazine derivatives, the dermacozines. The absolute stereochemistry of dermacozine D (4) was determined as S by a combination of CD spectroscopy and electronic structure calculations. Dermacozines F (6) and G (7) exhibited moderate cytotoxic activity against leukaemia cell line K562 with IC50 values of 9 and 7 mM, respectively, while the highest radical scavenger activity was observed for dermacozine C (3) with an IC50 value of 8.4 mM.
Research Authors
Wael M. Abdel-Mageed1,2, Bruce F. Milne3, Marcell Wagner4, Marc Schumacher5, Peter Sandor6, Wasu Pathom-aree7, Michael Goodfellow7, Alan T. Bull8, Koki Horikoshi9, Rainer Ebel1, Marc Diederich5, Hans-Peter Fiedler4, Marcel Jaspars1
Research Department
Research Journal
Org. Biomol. Chem.
Research Rank
1
Research Vol
Vol. 8
Research Year
2010

Laurefurenynes A–F, new Cyclic Ether Aceto-genins from a Marine Red Alga, Laurencia sp.

Research Abstract
We report here on the discovery and structure determination of three new diastereomeric pairs of cyclic ether acetogenins, laurefurenynes A–F, isolated from the aqueous extract of the alga Laurencia sp. collected in the Philippines. Extensive use was made of NMR spectroscopic data and high resolution MS to determine the structures of the pure compounds. The most stable and the lowest energy conformation was determined using molecular modelling, and their cytotoxic activity was tested against different tumour cells, a significant indication that laurefurenyne C and F are moderately cytotoxic, but non selective whilst the others are inactive.
Research Authors
Wael M. Abdel-Mageed1,2, Rainer Ebel2, Fred A. Valeriote3, Marcel Jaspars2
Research Department
Research Journal
Tetrahedron.
Research Rank
2
Research Vol
Vol. 66
Research Year
2010

Targeting the inflamed colonic mucosa of rats by using novel nanoparticulate delivery system

Research Authors
Makhlof A., Tozuka Y., Takeuchi H.
Research Department
Research Journal
The 129th Annual Meeting of the Pharmaceutical Society of Japan, Mar. 26-28, 2009, Kyoto, Japan
Research Member
Abdallah Mahmoud Hassanen Makhlof
Research Rank
3
Research Year
2009

Nanoparticle preparation of active pharmaceutical ingredients (APIs) by emulsion solvent diffusion method with Cyclodextrins

Research Authors
Makhlof A., Tozuka Y., Miyazaki Y., Takeuchi H.
Research Department
Research Journal
The 3rd Asian Particle Technology Symposium, Sep. 2-5, 2007, Beijing, China.
Research Member
Abdallah Mahmoud Hassanen Makhlof
Research Rank
3
Research Year
2007

Cyclodextrins as stabilizers for preparation of drug nanocrystals by the emulsion solvent diffusion method

Research Authors
Makhlof A., Miyazaki Y., Tozuka Y., Takeuchi H.
Research Department
Research Journal
The 45th Symposium on Powder Science and Technology, Oct. 29-31, 2007, Okayama, Japan.
Research Member
Abdallah Mahmoud Hassanen Makhlof
Research Rank
3
Research Year
2007

Colon-specific delivery of anti-inflammatory drug in inflammatory bowel disease using pH-sensitive nanospheres

Research Authors
Makhlof A., Tozuka Y., Takeuchi H.
Research Department
Research Journal
The 23rd Annual Meeting of the Academy of Pharmaceutical Science and Technology, May 20-22, 2008, Sapporo, Japan.
Research Member
Abdallah Mahmoud Hassanen Makhlof
Research Rank
3
Research Year
2008

Cyclodextrins as stabilizers for the preparation of drug nanocrystals by the emulsion solvent diffusion method

Research Abstract
Cyclodextrins (CyDs) were employed as protective stabilizers for the preparation of surfactant-free nanocrystals of indomethacin (IMC) by using the emulsion solvent diffusion method. The effect of changing the type and concentration of CyDs on the formation of IMC nanocrystals was investigated. Dispersions were freeze-dried to characterize the size, shape, nanoparticle yield, crystallinity, and dissolution behavior of the obtained particles. Submicron-sized particles of IMC with average diameters in the range of 300-500 nm were obtained by incorporating α-, β-, or γ-CyD in the outer phase of the primary emulsions. Quantitative determination demonstrated that more than 80% of IMC was recovered as fine particles smaller than 0.8 µm. The powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses of the freeze-dried samples confirmed the polymorphic change of IMC to the meta-stable form. A significant enhancement in the dissolution rate of IMC nanocrystals was observed when compared to the commercial powder.
Research Authors
Makhlof A., Miyazaki, Y., Tozuka Y., Takeuchi H.
Research Department
Research Journal
Int. J. Pharm.
Research Member
Abdallah Mahmoud Hassanen Makhlof
Research Rank
1
Research Vol
357
Research Year
2008

Mucoadhesive drug carriers and polymers for effective drug delivery

Research Abstract
The concept of mucoadhesion for the design of non-invasive drug delivery systems gained increasing attention in recent years. Within the current review, various mucoadhesive polymers, including poly(acrylates), chitosan, thiolated polymers and others, as well as their use in mucosal drug delivery are discussed. An emphasis has been put on the development of mucoadhesive formulations, and in particular on recently developed micro- and nanoparticulate systems. Moreover, the applications of the mucadhesive carrier systems for different administration routes such as the oral, nasal, pulmonary and ocular route are discussed.
Research Authors
Makhlof A., Werle M., Takeuchi H.
Research Department
Research Journal
J. Drug Deliv. Sci. Technol.
Research Member
Abdallah Mahmoud Hassanen Makhlof
Research Rank
1
Research Vol
18
Research Year
2008
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