Wael M. Abdel-Mageed

Organic structure determination using atomic-resolution scanning probe microscopy

Nature offers a huge and only partially explored variety of small molecules with potential pharmaceutical applications. Commonly used characterization methods for natural products include spectroscopic techniques such as nuclear magnetic resonance spectroscopy and mass spectrometry. In some cases, however, these techniques do not succeed in the unambiguous determination of the chemical structure of unknown compounds. To validate the usefulness of scanning probe microscopy as an adjunct to the other tools available for organic structure analysis, we used the natural product cephalandole A, which had previously been misassigned, and later corrected. Our results, corroborated by density functional theory, demonstrate that direct imaging of an organic compound with atomic-resolution force microscopy facilitates the accurate determination of its chemical structure. We anticipate that our method may be developed further towards molecular imaging with chemical sensitivity, and will become generally useful in solving certain classes of natural product structures.

Dermacozines, a new phenazine family from deep-sea dermacocci isolated from a Mariana Trench sediment.

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 IC(50) values of 9 and 7 microM, respectively, while the highest radical scavenger activity was observed for dermacozine C (3) with an IC(50) value of 8.4 microM.

Abyssomicins from the South China Sea deep-sea sediment Verrucosispora sp.: natural thioether michael addition adducts as antitubercular prodrugs

Tuberculosis (TB) is a leading cause of death in the world today, and is exacerbated by the prevalence of multi- (MDR-TB), extensively (XDR-TB), and totally (TDR-TB) drug resistant strains. Despite the threat to human health, existing frontline TB therapeutics remain constrained to a handful of vintage antibiotics prescribed in a combinatorial format to achieve efficacy. The current shortfall in antitubercular drugs demands urgent attention, to develop new antibiotics effective against all strains of tuberculosis.

Antiparasitic antioxidant phenylpropanoids and iridoid glycosides from Tecoma mollis.

A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1-7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1-8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed for compound (7) with an IC₅₀ value of 6.71 μg/ml, using pentamidine and amphotericin B as drug controls. Compound (5) exhibited moderate antimalarial activity (45% inhibition) against chloroquine sensitive (D6) clones of Plasmodium falciparum.

Antimicrobial Antioxidant Daucane Sesquiterpenes from Ferula hermonis Boiss

Seventeen daucane sesquiterpenoid esters, including a new one (4), were isolated from the root of Ferula hermonis Boiss. The structures of the isolated compounds were elucidated on the basis of spectroscopic evidence and correlated with known compounds. The relative stereochemistry of the new compound was determined using 2D NOESY and the most stable and the lowest energy conformation was determined using molecular modelling. The antimicrobial activity was evaluated by determination of MIC using the broth microdilution method against six bacterial strains and one fungal strain (Pseudomonas aeruginosa PAO1, Escherichia coli, Bacillus subtilis ATCC6633, Mycobacterium bovis BCG Pasteur, Mycobacterium tuberculosis H37Rv, Staphylococcus aureus ATCC6538 and Candida albicans SC5314). There was a significant indication that compounds 15, 16, 17 demonstrated potent activity against Gram +ve (S. aureus, B. subtilis), as well as Mycobacterium strains M. bovis BCG and M. tuberculosis H37Rv. None of the isolated compounds exhibited a significant antifungal activity. In the antioxidant study using the DPPH assay method, the highest radical scavenging activity was observed for compounds 15, 16, 17. Copyright

Dermacozines H-J Isolated from a Deep-Sea Strain of Dermacoccus abyssi from Mariana Trench Sediments

Dermacoccus abyssi sp. nov. strains MT1.1 and MT1.2 are actinomycetes isolated from a Mariana Trench sediment at a depth of 10 898 m. The fermentation process using complex media led to the production of three new pigmented heteroaromatic (oxidized and reduced) phenazine compounds, dermacozines H-J (1-3). Extensive use was made of 1D and 2D NMR experiments and high-resolution MS to determine the structures of the compounds. The new dermacozines showed radical scavenging activity, and the highest activity was observed for dermacozine H (1), with an IC50 value of 18.8 μM.

Caesanines A–D, New Cassane Diterpenes with Unprecedented N Bridge from Caesalpinia sappan

Serial antibacterial furanoditerpenes caesanines A-D (1-4), possessing a cassane-type diterpenoid skeleton with an unusual N bridge between C-19/C-20, were identified from a Chinese herb Caesalpinia sappan Linn. In addition, caesanine D (4) showed the first class of dicassane diterpenoid ethers. Their structures were determined by different spectroscopic methods and ECD calculation. Caesanines A and B exhibited strong activities against MRSA suggesting a promising entry point for the development of anti-infective drugs.

Antimicrobial activity of latex silver nanoparticles using Calotropis procera

ABSTRACT Objective To synthesize silver nanoparticles (AgNPs) by green methods using serum latex of Calotropis procera at 80 °C and evaluate them against bacteria, dermatophytes and phytopathogenic fungi comparing with the activity of untreated latex. Methods The synthesis of AgNPs was performed by mixing 3% latex serum extract with the same volume of silver nitrate (2 mmol/L) solution in round flask and heating in water bath at 80 °C. Characterization of silver particles were determined using UV-vis spectrophotometer, transmission electron microscopy (TEM), X-ray diffraction and Fourier transform infrared spectroscopy. The antimicrobial activity of the green synthesized AgNPs was determined against bacteria, dermatophytes and phytopathogenic fungi and compared to the crude untreated latex by agar-well diffusion methods. Results Biosynthesis of latex silver nanoparticles was successfully obtained by green method. The formation of AgNPs has been confirmed by UV-vis, TEM microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. TEM analysis showed that synthesized AgNPs are highly stable spherical shaped particles, well dispersed with a diameter ranged from 4 nm up to 25 nm and an average size of 12.33 nm. AgNPs showed strong antibacterial activity against Gram-negative bacteria ( Escherichia coli , Pseudomonas aeruginosa and Serratia sp.) and antifungal activity against Trichophyton rubrum , Candida albicans and Aspergillus terreus . Conclusions It can be concluded that serum latex of Calotropis procera was found to display strong potential for the synthesis of AgNPs as antimicrobial agents through rapid reduction of silver ions (Ag + to Ag 0 ). The green synthesized AgNPs were found to show higher antimicrobial efficacy than crude latex.

Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity

The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC50 values of 11.9 and 9.2μM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC50 values of 1.1 and 2.0μM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay.

Antioxidant and antiapoptotic activities of Calotropis procera latex on Catfish (Clarias gariepinus) exposed to toxic 4-nonylphenol.

Calotropis procera L. is known as medicinal plant. The Phytochemical analyzes of its latex revealed that it possessed antioxidants, namely terpenes, phenolic compounds and cardenolides, flavonoids and saponins, while tannins, alkaloids and resin were absent in moderate to high concentration. In the present study, the role of latex of Calotropis procera as antioxidant and antiapoptotic was reported. To carry out this aim, fishes were exposed to 100 µg l(-1) 4-nonylphenol as chemical pollutant. The enzymes, superoxidase dismutase, catalase, acetlycholinstrase (AchE), glutathione s-transferase, cortisol, G6PDH) and apoptotic cells increased significantly (p<0.05) accompanied by irregular disturbance of (Na(+), K(+)) ions in the presence of 4-nonylphenol. On the other hand, these enzymes, ions, and apoptotic cells decreased normally and significantly (p<0.05) in the presence of latex. Total phenol content, total capacity antioxidant, reducing power decrease significantly (p<0.05) in the presence of 4-nonylphenol and increase normally in the presence of latex. Latex was used for the first time to protect catfish after 4-nonylphenol exposure. Our study confirms that crude latex of Calotropis procera possessed antioxidant and antiapoptotic activities against the toxicity of 4-Nonylphenol.