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Nine flavonol oligosides of quercetin and kaempferol with glucose, xylose, and rhamnose as sugars were isolated from the seeds of Aesculus hippocastanum L. (Hippocastanaceae). Five of them are new compounds (2 trisaccharides, 1 bisdesmoside, a nicotinic and a indolinone hydroxyacetic acid ester of the bisdesmoside). Their structures were elucidated mainly using (1)H- and (13)C-NMR techniques.

Two new (3, 4) and two known (1, 2) genuine acylated bisdesmosidic triterpenoid glycosides of polygalacic acid (2 beta, 3 beta, 16 alpha, 23-tetrahydroxyolean-12-en-28-oic acid) were isolated from the aerial parts, as well as from the roots, of Solidago virgaurea L. subsp. virgaurea. The structures of these esters were elucidated as 4-O-fucopyranosyl-acylated compounds (1, 2, 3, 4) of 28-[O-alpha-L-rhamnopyranosyl-(1-->3)-O-beta-D-xylopyranosyl- (1-->4)-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-fucopyranosyl]-glycosid es of 3-O-[beta-D-glucopyranosyl]-polygalacic acid (5), and 3-O-[O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl]- polygalacic acid (6).

Trypanosomiasis (also known as sleeping sickness), an important parasitic disease caused by Trypanosoma brucei, is considered as a neglected disease that reemerged over the last few decades. This fact necessitates the search and development of new drugs to target this disease. In our continuous search for new and biologically active natural products for medicinal applications or as leads for the development of new therapies, fungal endophytes have proven to be a promising vast resource of unique metabolites with great pharmacological potential. In this study we investigated an endophytic Penicillium sp. which was isolated from stem tissues of Limonium tubiflorum (Rutaceae) growing in Egypt. Chemical investigation of the fungal extract yielded four new metabolites, including a new bianthrone (1), two new curvularin derivatives (2 and 3), as well as a new sulfinylchromone (4), in addition to 13 known metabolites (5-17). All structures were assigned by comprehensive spectral analysis (1D and 2D NMR) and mass spectrometry. Some of the isolated constituents proved active against T. brucei with MIC values ranging from 4.9 to 9.7 µM.

Protein kinases, which function as components of signal transduction pathways, play a central role in diverse biological processes, such as control of cell growth, metabolism, differentiation, and apoptosis [1]. Identification of the key roles of protein kinases in cancer has led to extensive efforts to develop kinase inhibitors for the treatment of a wide range of cancers [2]. In continuation of our efforts to discover natural protein kinase inhibitors we studied extracts of liquid and rice cultures of the fungal endophyte Alternaria sp. isolated from the Egyptian medicinal plant Polygonum senegalense. Chromatographic separation of the extracts yielded the known compounds alternariol (1), alternariol 5-O-methyl ether (2), altenusin (3), 2,5-dimethyl-7-hydroxychromone (4), tenuazonic acid (5), altertoxin I (6), talaroflavone (7), and altenuene (8), in addition to seven new metabolites (9-15). The structures of the compounds were unambiguously established on the basis of NMR spectroscopic and mass spectrometric data. Compounds 1-3, 9, and 12 showed cytotoxic activity toward L5178Y mouse lymphoma cell line with EC50 values ranging from 1.7 to 7.8µg/mL. When analyzed in vitro for their inhibitory potential against 24 different protein kinases, compounds 1-3, 6, 9, and 11-13 inhibited several of these enzymes (IC50 values 0.22-9.8µg/mL).

The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded eight new secondary metabolites, alterporriol F, alterporriol G and its atropisomer H, alterporriol I and its atropisomer J, altersolanol K, altersolanol L and stemphypyrone, beside eight known compounds. The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H exhibited considerable cytotoxicity against L5178Y cells with an EC50 value of 2.7 µg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for protein kinase inhibitory activity in an assay involving 24 different kinases. Compounds methylalaternin, macrosporin, altersolanol A and the mixture of alterporriol G and H were the most potent and also selective inhibitors, displaying EC50 values between 0.64 and 1.4 µg/mL toward individual kinases.

A detailed analysis of a Philippine specimen of the marine echinoderm Comanthus sp. yielded fifteen compounds including four anthraquinones identified as 1'-deoxyrhodoptilometrin (1) along with its 6-O-sulfate derivative (3), and rhodoptilometrin (2) with its 6-O-sulfate derivative (4). In addition five naphthpyrones including comaparvin (5), 6-methoxycomaparvin (6), 6-methoxycomaparvin-5-methylether (7), 6-methoxycomaparvin-5-methylether-8-O-sulfate (8), and 6-hydroxycomaparvin-8-O-sulfate (9) were likewise isolated and identified. Further compounds include steroids and a nucleoside derivative. The structures of the isolated compounds were unambiguously elucidated based on HRESIMS analysis, 1D and 2D NMR, and by comparison with the literature. For compounds 2 and 4 the absolute configurations were identified for the first time using the Mosher reaction. Both compounds are (S)-(-) enantiomers. All isolated compounds were evaluated for their cytotoxic activities against cancer cells using the (MTT) assay and compared to the well known marine cancer drug candidate kahalalide F (EC50=6.3 µg/mL). 1'-Deoxyrhodoptilometrine (1) and an unseparable mixture of comaparvin (5) and 6-methoxycomaparvin (6) exhibited pronounced cytotoxicity against mouse lymphoma L5178Y cells with EC50 values of 2.3 and 5.2 µg/mL, respectively.

ORTHOSIPHON ARISTATUS (Orthosiphonis folium DAB 9) was studied with regard to its phenolic constituents. Twenty compounds were isolated and identified on the basis of their spectral characteristics. The compounds included nine lipophilic flavones, two flavonol glycosides, and nine caffeic acid derivatives. The presence of the recently reported methylripariochromene A could not be confirmed. All compounds identified were quantified by HPLC. The caffeic acid derivatives including the major compounds rosmarinic acid and 2,3-dicaffeoyltartaric acid (67% of total identified phenolics) predominated over the flavones (33%) in an aqueous MeOH extract. The predominance of the caffeic acid derivatives was even more pronounced in a hot water extract (94.5% of total identified phenolics) that was comparable to a herbal tea.

Three new cyanogenic diglycosides of the mandelonitrile series have been isolated from fruits of ANTHEMIS CAIRICA (Compositae) and their structures identified by degradation and spectral methods mainly (1)H-NMR, (13)C-NMR, FAB-MS. Minor compounds are 2-beta-primeverosyloxy-2-phenyl-2S-acetonitrile (epilucumin) and its 4''-p(beta-D-glucopyranosyloxyl-(E)cinnamate; the main compound is the 4''-p(beta-primeverosyloxy)-(E)cinnamate of epilucumin.

A cell suspension culture of AGERATINA ADENOPHORA was shown to yield several novel chromene and benzofuran derivatives in minute amounts that were different to the compounds found in seedlings of the same species. The structure elucidation of the new compounds is described. When two of the seedling chromenes (demethoxyencecalin and demethylencecalin) were fed to the cell suspension culture, one biotransformation product each was obtained in high yields (80%) that originated from a hydroxylation at one of the geminal methyl groups of the chromene heterocycle. These products accumulated largely in the growth media even though the presence of cells was necessary for the biotransformations to occur. When the third seedling chromene (encecalin) was fed to the cell auspension culture, no significant biotransformation was noted but several of the benzofurans present as cell culture metabolites showed a significantly increased accumulation in the growth media of the treated cultures. This increased accumulation of benzofurans was found to be inducible also by adding yeast extract to the cell culture. The metabolism of chromenes and bezofurans in the cell suspension culture is discussed.

Cell cultures of THUJA OCCIDENTIALIS L. were found to biosynthesize various mono- and diterpenes when grown on B5-medium. The identification of the constituents was achieved mainly by capillary GLC-MS using fused silica columns and E.I.-mass spectrometry. Monoterpenes of the menthane type were only isolated from the culture medium whereas diterpenes were found in the cell extracts. Thujaplicin derivatives, monoterpenes of an irregular type, were detected in the medium as well as in the cells. Major differences were found between the terpene composition of the cell culture extracts and those from THUJA leaves. The cell cultures accumulated some compounds which are presently unknown as constituents of THUJA plants. On the other hand, the cultures were evidently unable to synthesize the thujone type of monoterpenes.

Root cultures of Eupatorium cannabinum were shown to accumulate a plethora of benzofuran derivatives. The benzofurans were qualitatively and quantitatively identical or similar to those found in roots of differentiated plants. Seven benzofurans including a new natural product were isolated and identified. The structure elucidation of the new compound is described. Studies on the biosynthesis of the benzofurans were carried out by feeding 14C-labelled compounds and stable isotopes to the root cultures of E. cannabinum. The results obtained established that the aromatic ring, as well as the C-acetyl substituent linked to the aromatic ring, originate from the shikimic acid pathway via phenylalanine and cinnamic acid. The C-acetyl substituent was shown to arise directly from the phenylpropanoid side chain.