Serge Fotso

Reactions of the melatonin metabolite AMK (N1-acetyl-5-methoxykynuramine) with reactive nitrogen species: Formation of novel compounds, 3-acetamidomethyl-6-methoxycinnolinone and 3-nitro-AMK

Abstract:u2002 The melatonin metabolite N1‐acetyl‐5‐methoxykynuramine (AMK) was found to be unstable in air when adsorbed on a thin‐layer silica gel chromatography plate, a result that is in good agreement with the relatively high reactivity of this compound. Three novel main products were separated from the reaction mixture and identified by mass spectrometry and nuclear magnetic resonance data as: (i) 3‐acetamidomethyl‐6‐methoxycinnolinone (AMMC), (ii) 3‐nitro‐AMK (AMNK, N1‐acetyl‐5‐methoxy‐3‐nitrokynuramine), and (iii) N‐[2‐(6‐methoxyquinazolin‐4‐yl)‐ethyl]‐acetamide (MQA). AMMC and AMNK are shown to be nonenzymatically formed also in solution, by nitric oxide (NO) in the first case, and by a mixture of peroxynitrite and hydrogen carbonate, in the second one. The use of three different NO donors, PAPA‐NONOate, S‐nitroso‐N‐acetylpenicillamine and sodium nitroprussiate led to essentially the same results, with regard to a highly preferential formation of AMMC; AMNK was not detected in these reaction systems. Competition experiments with the NO scavenger N‐acetylcysteine indicate a somewhat lower reactivity compared with the competitor. Peroxynitrite led to AMNK formation in the presence of physiological concentrations of hydrogen carbonate at pH 7.4, but not in its absence, indicating that nitration involves a mixture of carbonate radicals and NO2, formed from the peroxynitrite‐CO2 adduct. No AMMC was detected after AMK exposure to peroxynitrite. Both AMNK and AMMC exhibited a much lower reactivity toward 2,2′‐azino‐bis‐(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) cation radicals than did AMK. In a competition assay for hydroxyl radicals, AMMC showed prooxidant properties, whereas AMNK was a moderate antioxidant. AMMC and AMNK should represent relatively stable physiological products, although their rates of synthesis are still unknown and may be low. Formation of these compounds may contribute to the disappearance of AMK from tissues and body fluids.

N-carboxamido-staurosporine and selina-4(14),7(11)-diene-8,9-diol, new metabolites from a marine Streptomyces sp.

In our screening of micro-organisms for novel bioactive natural products, a new staurosporinone, N-carboxamido-staurosporine (1c), and a new sesquiterpene, (5S,8S,9R,10S)-selina-4(14),7(11)-diene-8,9-diol (2a), were isolated from the culture broth of the marine-derived Streptomyces sp. QD518. Their structures were determined by spectroscopic methods and by comparison of the NMR data with those of structurally related known natural products, which were isolated from the same strain.

Naturally Occurring Anthracyclines

The present article gives an overview of the natural occurring anthracyclines and anthracyclinonesreported from microorganisms. A general description, discussion of their physicochemical properties,including NMR increments, and their structural classification are reported. In addition to a compilationof their sugar moieties, an exhaustive list of naturally occurring anthracyclines and anthracyclinoneshas been added.

Kettapeptin: Isolation, Structure Elucidation and Activity of a New Hexadepsipeptide Antibiotic from a Terrestrial Streptomyces sp.

The ethyl acetate extract of the Streptomyces sp. isolate GW99/1572 exhibited significant biological activity against Gram-positive bacteria and delivered kettapeptin (1), a new hexadepsipeptide antibiotic of the azinothricin type. The structure was elucidated by various 1D and 2D NMR techniques, mass spectrometry and by comparison of the NMR data with those of closely related antibiotics. The absolute configuration of the compound was derived by crystal structure analysis and by comparison with the optical rotation data of related compounds.

Aqabamycins A–G: novel nitro maleimides from a marine Vibrio species: II. Structure elucidation *

The structures of secondary metabolites with antibacterial and cytotoxic activities produced by a marine Vibrio strain from the Red Sea were elucidated. Aqabamycin A (1a) and seven further nitro-substituted maleimide derivates named aqabamycins B–G (1b–f and 2) were obtained together with 12 known metabolites, 3-nitro-1H-indazole (3), indazole-3-carbaldehyde (4), 3-nitro-4-hydroxycinnamic acid, 4-hydroxycinnamic acid, 3-nitro-4-hydroxybenzaldehyde, phenyl-2-bis-indolylmethane (5a), turbomycin B (5b), vibrindole A (6), phenylacetic acid, 3-hydroxybenzoic acid, benzoic acid and 1,4-dithiane (7). Some of the known metabolites (for example, 3, 4 and 7) are described in this study for the first time as natural products. Their structures were elucidated based on 1D and 2D NMR, MS spectra and by comparison with synthetic material.

Niruriflavone, a new antioxidant flavone sulfonic acid from Phyllanthus niruri

A new flavone sulfonic acid 1 named niruriflavone was isolated from the 70% ethanolic extract of the whole plant of Phyllanthus niruri (Euphorbiaceae), together with 6,10,14-trimethyl-2- pentadecanone, hypophyllanthin, gallic acid, brevifolin carboxylic acid, methyl brevifolin carboxylate, isoquercetin, quercetin-3-O-β -D-glucopyranosyl(1→ 4)-α-rhamnopyranoside, corilagin, and isocorilagin, whose structures were determined by spectroscopic methods and comparison with published data. In an ABTS cation radical reduction assay, niruriflavone (1) exhibited potent radical scavenging properties. A biological test system based on bioluminescence of the dinoflagellate Lingulodinium polyedrum did not reveal any prooxidant properties of 1 at 50 μM.

Metabolites of the sea isolate of bacteria Streptomyces SP 6167

Sea isolate of Streptomyces sp. 6167 was found to produce four macrolide antibiotics feigrisolides A, B, and D, and dinactin. The chemical structures of the compounds were determined using 1D and 2D NMR spectrometry and electrospray mass spectrometry (ESMS). It was shown that the feigrisolides are cytotoxic to Ehrlich carcinoma tumor cells and to egg-cells of the sea urchin Strongylocentrotus intermedius and antimicrobial to the bacteria Bacillus cereus and Escherichia coli.

2-Hydroxy-luisol A, a New Quinone-derived Tetraol from a Marine Streptomyces sp. and Oxidation Products of Luisol A*

In addition to luisol A (1a), luisol B (2), and aloesaponarin II, the marine streptomycete B7617 produced a new derivative of 1a, 2-hydroxy-luisol A (1b). In an attempt to increase the biological activity, luisol A (1a) was oxidized and delivered with Jones reagent or by Swern oxidation the derivatives 3a/3b and 4a/4b, respectively, but none of these compounds showed antimicrobial or cytotoxic activities. All structure elucidations are based on 2D NMR analyses or were derived by comparison with published data. Graphical Abstract 2-Hydroxy-luisol A, a New Quinone-derived Tetraol from a Marine Streptomyces sp. and Oxidation Products of Luisol A*

Isolation, structure elucidation and activity of anthracycline acetates from a terrestrial Streptomyces sp.

The red coloured ethyl acetate extract of the Streptomyces sp. isolate GW37/3236 delivered the two new antibiotics 13-O-acetyl-bisanhydro-13-dihydrodaunomycinone (3c) and 4,13-O-diacetylbisanhydro- 4-O-demethyl-13-dihydrodaunomycinone (3d) and additionally several known compounds. The quinones 3c and 3d are the first naturally occurring quinone acetates. Their structures were derived by comparison of the NMR data with those of bisanhydro-13-dihydrodaunomycinone (3b) and by interpretation of the 2D NMR data accompanied by the molecular weight and formula. 2-Acetamido-3-hydroxybenzamide (5) was also isolated from the extract and was identified by comparison of the NMR data with those of 2-acetamidobenzamide and by 2D NMR correlations. 6,9,11- Trihydroxy-4-methoxy-5,12-naphthacenedione (4) is isolated for the first time as a natural product.

Juglorescein, Juglocombins and Juglochromans: Structure of Juglomycin Dimers from Streptomycetes

Novel juglomycin derivatives with a C28 skeleton were isolated from the Streptomyces strains 815 and GW4184. Juglorescein (1a) and juglocombin A (2a) and B (3a) are C,C dimers of juglomycin C (10) with a five membered ring between the two monomeric moieties. In the juglochromans A-D (4a, 5a, 6a, 6c), two juglomycin C (10) units are connected by C,C and C,O bonds forming a central isochroman or a chroman system. The structures of the new natural products were elucidated by detailed spectra analyses, by comparison of the NMR data with those of related compounds and by biosynthetic considerations. The new natural products were antimicrobially inactive.