Usama W. Hawas

Novel Bioactive Metabolites from a Marine Derived Bacterium Nocardia sp. ALAA 2000

Extracts of the Egyptian marine actinomycete, Nocardia sp. ALAA 2000, were found to be highly bioactive. It was isolated from the marine red alga Laurenica spectabilis collected off the Ras-Gharib coast of the Red Sea, Egypt. According to detailed identification studies, the strain was classified as a member of the genus Nocardia. The cultivation and chemical analysis of this species yielded four structurally related compounds namely, chrysophanol 8-methyl ether (1), asphodelin; 4,7′-bichrysophanol (2) and justicidin B (3), in addition to a novel bioactive compound ayamycin; 1,1-dichloro-4-ethyl-5-(4-nitro-phenyl)-hexan-2-one (4) which is unique in contain both chlorination and a rarely observed nitro group. The compounds were isolated by a series of chromatographic steps and their structures of 1~3 secured by detailed spectroscopic analysis of the MS and NMR data whereas that of 4 was elucidated by single crystal X-ray diffraction studies. These compounds displayed different potent antimicrobial activity against both Gram-positive and Gram-negative bacteria as well as fungi with MIC ranging from 0.1 to 10 μg/ml.

An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.

Bioactive anthraquinones from endophytic fungus Aspergillus versicolor isolated from red sea algae

The marine fungus Aspergillus versicolor was isolated from the inner tissue of the Red Sea green alga Halimeda opuntia. The fungus was identified by its morphology and 18s rDNA. Cultivation of this fungal strain led to a new metabolite named isorhodoptilometrin-1-methyl ether (1) along with the known compounds emodin (2), 1-methyl emodin (3), evariquinone (4), 7-hydroxyemodin 6,8-methyl ether (5), siderin (6), arugosin C (7), and variculanol (8). The structures were elucidated on the basis of NMR spectroscopic analysis and mass spectrometry. The biological properties of ethyl acetate extract and compounds 1–3 and 6–8 were explored for antimicrobial activity, anti-cancer activity and inhibition of Hepatitis C virus (HCV) protease.

Two new flavonoids from Origanum vulgare

In addition to the major constituents apigenin, luteolin, salvagenin, cirsimartin, diosmetin, desmethoxycentauridin, 5-hydroxy-6,7,3′,4′-tetramethoxy-abigenin, apigenin 7-O-glucoside, luteolin 7-O-glucoside, luteolin 7-O-glucoside-6′′-methylester, two new flavonoids were isolated, in minor concentration, and identified as luteolin 7-O-α-L-rhamnoside-4′-O-β-D-glucoside and quercetin 3-O-β-D-glucoside-4′-O-α-L-rhamnoside from the methanolic extract of Origanum vulgare L. The structures were determined by conventional analytical methods and confirmed by MS and NMR spectral analysis.

NMR spectral analysis of flavonoids from Chrysanthemum coronarium

Naringenin 5-O-glucoside, apigenin 7-O-glucoside, luteolin 7-O-glucoside, kaempferol 3-O-glucoside, quercetin 3-O-glucoside, apigenin, luteolin, kaempferol, and quercetin, nine flavonoid derivatives, were isolated for the first time from the aqueous methanolic extract of the aerial parts of Chrysanthemum coronarium. Their structures were elucidated on the basis of chemical and spectroscopic (UV, 1H, 13C NMR) analyses. 1-and 2-dimensional NMR spectroscopy of the rare naringenin 5-O-glucoside have been recorded and assigned for the first time. The flavonoid glucosides from Chrysanthemum coronarium showed week activity against Poliovirus I and Adenovirus type 7.

Antioxidant activity of brocchlin carboxylic acid and its methyl ester from Chrozophora brocchiana

The analogue of brevifolin carboxylic acid and its methyl ester were isolated and identified from the aqueous ethanolic extract of the leaves of Chrzophora brocchiana in addition to eight known compounds identified as gallic acid, methyl and ethyl gallate, ellagic acid, monomethoxy and methylenedioxy ellagic acid, apigenin 7-O-glucoside and luteolin 7-O-glucoside. The structures were determined primarily by ESI-MS and NMR spectroscopy. The assignment of NMR signals was preformed by means of 1H–H COSY, HMQC and HMBC experiments. The antioxidant activity of the new compounds was determined by checking the scavenging activity against DPPH free radical.

A New 8-Hydroxy Flavone O-Xyloside Sulfate and Antibacterial Activity from the Egyptian Seagrass Thalassia hemprichii

A new 8-hydroxy flavone O-xyloside sulfate, isoscutellarein 7-O-β-xyloside-2′′-O-sulfate, along with four known metabolites, were isolated and identified from seagrass, Thalassia hemprichii, collected from the Egyptian Red sea coast. The structures of the isolated compounds were established by chemical degradation and spectral analysis. The crude extract and the new compound displayed different potent antimicrobial activity against both Gram-positive and Gram-negative bacteria as well as fungi with MIC ranging from 0.1 to 10 μg/mL.

In vitro antioxidant and antiproliferative activities of flavonoids from Ailanthus excelsa (Roxb.) (Simaroubaceae) leaves.

The present study aimed to investigate the chemical composition, and the antioxidant and antiproliferative activities of Ailanthus excelsa, a plant used in Egyptian traditional medicine. Chromatographic separation of a methanol extract of A. excelsa leaves yielded four fl avones, namely apigenin (1), apigenin 7-O-β-glucoside (2), luteolin (3), and luteolin 7-O-β-glucoside (4), and seven fl avonols, namely kaempferol (5), kaempferol 3-O-α-arabinoside (6), kaempferol 3-O-β-galactoside (7), quercetin (8), quercetin 3-O-α-arabinoside (9), quercetin 3-O-β- galactoside (10), and quercetin 3-O-rutinoside (11). The A. excelsa extract tested in different in vitro systems (DPPH and FRAP assays) showed significant antioxidant activity. The potential antiproliferative activity of the A. excelsa extract and isolated flavonoids against five human cancer cell lines such as ACHN, COR-L23, A375, C32, and A549 was investigated in vitro by the SRB assay in comparison with one normal cell line, 142BR. The extract exhibited the highest inhibitory activity against C32 cells with an IC50 value of 36.5 μg ml-1. Interesting activity against COR-L23 was found with 10 (IC50 value of 3.2 μg ml-1). Compounds 1 and 3 inhibited cell growth in both amelanotic melanoma and malignant melanoma cells.

A new flavone glucoside from Stachys aegyptiaca

In addition to 5,7,3′-trihydroxy-6,4′-dimethoxyflavone, 5,7,3′-trihydroxy-6,8,4′-trimethoxyflavone, isoscutellarein, luteolin, and luteolin-7-O-glucoside, the methanol extract of the aerial parts of Stachys aegyptiaca yielded a new flavone identified as luteolin 3′,4′-dimethylether-7-O-β-D-glucoside on the basis of chemical and spectroscopic methods.

Induction of Caspase-8 and Death Receptors by a New Dammarane Skeleton from the Dried Fruits of Forsythia koreana

A new naturally occurring compound based on the dammarane skeleton, i.e. cabralealactone 3-acetate-24-methyl ether, was isolated from the aqueous methanolic extract of Forsythia koreana fruits, along with eight known compounds: cabralealactone 3-acetate, ursolic acid, arctigenin, arctiin, phillyrin, rutin, caffeic acid, and rosmarinic acid. The identifi cation of the isolated compounds was based on their spectral analysis including: HREI-MS, 1D and 2D NMR spectroscopy. The selected compounds and the aqueous methanolic extract were evaluated for their cytotoxic activity against human solid tumour cell lines. Cabralealactone 3-acetate-24-methyl ether and ursolic acid were found to be active against human breast cancer cells (MCF-7). The cytotoxicity was associated with the activation of caspase-8, the induction of the death receptors DR4 and DR5, as well as DNA fragmentation, and was thus due to apoptosis rather than necrosis