Diversity of secondary metabolites from Genus Artocarpus (Moraceae)

Abstrak. Hakim A. 2010. Keanekaragaman metabolit sekunder Genus Artocarpus (Moraceae). Nusantara Bioscience 2:146-156. Beberapa spesies dari genus Artocarpus (Moraceae) telah diteliti kandungan bahan alamnya. Metabolit sekunder yang berhasil diisolasi dari genus Artocarpus terdiri dari terpenoid, flavonoid, stilbenoid, arilbenzofuran, neolignan, dan adduct Diels-Alder. Kelompok flavonoid merupakan senyawa yang paling banyak ditemukan dari tumbuhan Artocarpus. Senyawa flavonoid yang telah berhasil diisolasi dari tumbuhan Artocarpus memiliki kerangka yang beragam seperti calkon, flavanon, flavan-3-ol, flavon sederhana, prenilflavon, oksepinoflavon, piranoflavon, dihidrobenzosanton, furanodihidrobenzosanton, piranodihidrobenzosanton, kuinonosanton, siklolopentenosanton, santonolid, dihidrosanton. Kata kunci: Artocarpus, Moraceae, flavonoid, Diels-Alder, metabolit sekunder

Lack of complex I activity in human cells carrying a mutation in MtDNA-encoded ND4 subunit is corrected by the Saccharomyces cerevisiae NADH-quinone oxidoreductase (NDI1) gene

The gene for the single subunit, rotenone-insensitive, and flavone-sensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae (NDI1) can completely restore the NADH dehydrogenase activity in mutant human cells that lack the essential mitochondrial DNA (mtDNA)-encoded subunit ND4. In particular, the NDI1 gene was introduced into the nuclear genome of the human 143B.TK cell line derivative C4T, which carries a homoplasmic frameshift mutation in the ND4 gene. Two transformants with a low or high level of expression of the exogenous gene were chosen for a detailed analysis. In these cells the corresponding protein is localized in mitochondria, its NADH-binding site faces the matrix compartment as in yeast mitochondria, and in perfect correlation with its abundance restores partially or fully NADH-dependent respiration that is rotenone-insensitive, flavone-sensitive, and antimycin A-sensitive. Thus the yeast enzyme has become coupled to the downstream portion of the human respiratory chain. Furthermore, the P:O ratio with malate/glutamate-dependent respiration in the transformants is approximately two-thirds of that of the wild-type 143B.TK cells, as expected from the lack of proton pumping activity in the yeast enzyme. Finally, whereas the original mutant cell line C4T fails to grow in medium containing galactose instead of glucose, the high NDI1-expressing transformant has a fully restored capacity to grow in galactose medium. The present observations substantially expand the potential of the yeast NDI1 gene for the therapy of mitochondrial diseases involving complex I deficiency

Allosteric Inhibition of Factor XIIIa. Non-Saccharide Glycosaminoglycan Mimetics, but Not Glycosaminoglycans, Exhibit Promising Inhibition Profile

Factor XIIIa (FXIIIa) is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors. Yet, allosteric inhibition of FXIIIa is a paradigm that may offer a key advantage of controlled inhibition over orthosteric inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We reasoned that targeting a collection of basic amino acid residues distant from FXIIIa’s active site by using sulfated glycosaminoglycans (GAGs) or non-saccharide GAG mimetics (NSGMs) would lead to the discovery of the first allosteric FXIIIa inhibitors. We tested a library of 22 variably sulfated GAGs and NSGMs against human FXIIIa to discover promising hits. Interestingly, although some GAGs bound to FXIIIa better than NSGMs, no GAG displayed any inhibition. An undecasulfated quercetin analog was found to inhibit FXIIIa with reasonable potency (efficacy of 98%). Michaelis-Menten kinetic studies revealed an allosteric mechanism of inhibition. Fluorescence studies confirmed close correspondence between binding affinity and inhibition potency, as expected for an allosteric process. The inhibitor was reversible and at least 9-fold- and 26-fold selective over two GAG-binding proteins factor Xa (efficacy of 71%) and thrombin, respectively, and at least 27-fold selective over a cysteine protease papain. The inhibitor also inhibited the FXIIIa-mediated polymerization of fibrin in vitro. Overall, our work presents the proof-of-principle that FXIIIa can be allosterically modulated by sulfated non-saccharide agents much smaller than GAGs, which should enable the design of selective and safe anticoagulants

ZZE-Configuration of chromophore ß-153 in C-phycocyanin from Mastigocladus laminosus

The photochemistry of C-phycocyanin has been studied after denaturation in the dark. It shows an irreversible reaction which has characteristics of a Ζ,Ζ,Ε- to Z,Z,Z-isomerization of dihydrobilins. Its amplitude depends on the reaction conditions, with a maximum corresponding to 15% conversion of one of the three PC chromophores. This chromophore is suggested to be ß-153, for which recent X-ray data T. Schirmer, W. Bode, and R. Huber, J. Mol. Biol., submitted, show ring D being highly twisted out of the plane of the other rings. During unfolding, there is thus a probability of falling into the photochemically labile Z,Z,^-configuration

Mechanism and Application of Baker–Venkataraman O→C Acyl Migration Reactions

This literature review focuses on the O→C acyl migration of aryl esters to yield the corresponding 1,3-dicarbonyl products—a reaction known as the Baker–Venkataraman rearrangement—and outlines their subsequent transformations. The purpose of the review is to highlight the utility of the rearrangement which provides a key step in the synthesis of various heterocyclic motifs. The scope of the Baker–Venkataraman rearrangement is illustrated by way of numerous examples of its application, and in doing so, the review contains over 100 references and covers just over 100 years of the literature, from the first report of the rearrangement by Auwers in 1910 up to more recent examples in the past few years. 1 Introduction 2 Historical Perspective 3 Mechanism 4 Applications: General Routes to Heterocycles 4.1 Flavones and Flavanones 4.2 Xanthones 4.3 Chromones 4.4 Coumarins 4.5 Anthrapyran and Anthracyclin Antibiotics 4.6 Benzopyrans 5 The Retro-Baker–Venkataraman Rearrangement 6 Summary and Outloo

Betalains and phenolic compounds of leaves and stems of Alternanthera brasiliana and Alternanthera tenella

Betacyanins and phenolic compounds from acetonitrile:acidified water extracts of Alternanthera brasiliana and Alternanthera tenella were characterized and quantified using a high-performance liquid chromatography system coupled with diode array and electrospray mass spectrometry detection. Four betacyanins (amaranthine, isoamaranthine, betanin and isobetanin) were tentatively identified and quantified. Twenty eight phenolic compounds of four different families (hydroxybenzoic and hydroxycinnamic acids, flavones and flavonols) were separated and characterized on the basis of their accurate MS and MS/MS information out of which ten compounds were confirmed by authentic standards. These plant species could be considered as an especially rich source of natural bioactive compounds and potential food colorants. A. brasiliana showed the highest betacyanin and polyphenols content (89 μg/g and 35,243 μg/g, respectively). Among polyphenols, flavonols were the more abundant (kaempferol-glucoside, kaempferol-rutinoside and kaempferol-rhamnosyl-rhamnosyl-glycoside). Meanwhile, A. tenella showed a different polyphenols profile with flavones as major compounds (glucopyranosil-vitexin and vitexin). As a novelty, pentosyl-vitexin and pentosyl-isovitexin were detected for the first time in Alternanthera plants. Both A. brasiliana and A. tenella leaves showed high total polyphenol content and in vitro antioxidant activity (FRAP). These results provide an analytical base concerning the phenolic and betalains composition and the antioxidant properties of two members of the promising Alternanthera gender, for subsequent applications, such as functional food ingredients.Fil: Deladino, Lorena. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; ArgentinaFil: Alvarez, I.. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia y Tecnologia de Alimentos y Nutrición; EspañaFil: De Ancos, B.. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia y Tecnologia de Alimentos y Nutrición; EspañaFil: Sánchez Moreno, C.. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia y Tecnologia de Alimentos y Nutrición; EspañaFil: Molina García, A. D.. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia y Tecnologia de Alimentos y Nutrición; EspañaFil: Schneider Teixeira, Aline. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia y Tecnologia de Alimentos y Nutrición; Españ

Exploring the Phytochemical Landscape of the Early-Diverging Flowering Plant Amborella trichopoda Baill.

Although the evolutionary significance of the early-diverging flowering plant Amborella (Amborella trichopoda Baill.) is widely recognized, its metabolic landscape, particularly specialized metabolites, is currently underexplored. In this work, we analyzed the metabolomes of Amborella tissues using liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS). By matching the mass spectra of Amborella metabolites with those of authentic phytochemical standards in the publicly accessible libraries, 63, 39, and 21 compounds were tentatively identified in leaves, stems, and roots, respectively. Free amino acids, organic acids, simple sugars, cofactors, as well as abundant glycosylated and/or methylated phenolic specialized metabolites were observed in Amborella leaves. Diverse metabolites were also detected in stems and roots, including those that were not identified in leaves. To understand the biosynthesis of specialized metabolites with glycosyl and methyl modifications, families of small molecule UDP-dependent glycosyltransferases (UGTs) and O-methyltransferases (OMTs) were identified in the Amborella genome and the InterPro database based on conserved functional domains. Of the 17 phylogenetic groups of plant UGTs (A-Q) defined to date, Amborella UGTs are absent from groups B, N, and P, but they are highly abundant in group L. Among the 25 Amborella OMTs, 7 cluster with caffeoyl-coenzyme A (CCoA) OMTs involved in lignin and phenolic metabolism, whereas 18 form a clade with plant OMTs that methylate hydroxycinnamic acids, flavonoids, or alkaloids. Overall, this first report of metabolomes and candidate metabolic genes in Amborella provides a starting point to a better understanding of specialized metabolites and biosynthetic enzymes in this basal lineage of flowering plants

Development of arbuscular mycorrhizal fungi in the presence of different patterns of Trifolium repens shoot flavonoids

We tested the effects of the flavonoid 3-methoxi-5,6,7,8-hydroxy-4'hydroxy flavone (NMHTV) isolated from shoots of non arbuscular mycorrhizal (AM) inoculated clover, and of the flavonoids 5,6,7,8-hydroxy-3-methoxy flavone (MH-1); 5,6,7,8-hydroxy-4'- hydroxy flavone (MH-2); and 5,7-hydroxy-3,4'-methoxy flavone (MH-3); isolated from AM clover (Trifolium repens) shoots, on spore germination, hyphal length, hyphal branches and the number of cluster of auxiliary cells or the number of secondary spores (Presymbiotic stage) and on the number of entry points and the percentage of AM colonized root of tomato (Lycopersicum esculentum) by the AM fungi Gigaspora rosea, Giaspora margarita, Glomus mosseae and Glomus intraradices (Symbiotic stage). Non significant effects of the flavonoids isolated from the shoot of mycorrhizal colonized clover on the presymbiotic and symbiotic stages of Gigaspora and Glomus endophytes were found. The flavonoid NMHTV isolated from non AM clover shoot, did not affect the percentage of germination of spores but significantly increased (P < 0.05) the other steps of the presymbiotic stage of Gi. margarita spores when 2 μM concentration was used. The symbiotic stage of Gi. margarita was also significantly increased when 2 μM of the flavonoid NMHTV was applied. This flavonoid had no effect on the presymbiotic development of G. mosseae, G. intraradices and Gi. rosea except when 8 μM concentration was used, which inhibited the hyphal length of Gi. rosea. These results suggest the possible implication of the flavonoid NMHTV in the susceptibility of tomato roots to the AM formation by Gi. margarita. The absence of stimulation of the AM presymbiotic and symbiotic stages in tomato by exogenous application of the newly synthesized flavonoids MH-1, MH-2, and MH-3, in clover shoots after AM colonization, indicated that the autorregulation of the AM symbiosis can be, at least partially, due to the disappearance of flavonoids in AM colonized plants that stimulated the AM symbiosis.Fil: Scervino, Jose Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Ponce, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Della Mónica, Ivana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Vierheilig, Horst. Universitat Fur Bodenkultur Wien; Austria. Consejo Superior de Investigaciones Científicas. Estación Experimental del Zaidín; EspañaFil: Ocampo, Juan Antonio. Consejo Superior de Investigaciones Científicas. Estación Experimental del Zaidín; EspañaFil: Godeas, Alicia Margarita. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Pb2+, Cu2+, Zn2+, Mg2+ and Mn2+ reduce the affinities of flavone, genistein and kaempferol for human serum albumin in vitro

Flavone (Fl), genistein (Gen) and kaempferol (Kol) were studied for their affinities towards human serum albumin (HSA) in the presence and absence of Pb2+,Cu2+,Zn2+,Mg2+ and Mn2+. The fluorescence intensities of HSA decreased with increasing concentration of the three flavonoids. Kaempferol resulted in a blue-shift of the λem of HSA from 336 to 330 nm; flavone showed an obvious red-shift of the λem of HSA from 336 to 342 nm; genistein did not cause an obvious blue-shift or red-shift of the λem of HSA. However, the extents of λem-shifts induced by the flavonoids in the presence of metal ions were much bigger than that in the absence of mental ions. Pb2+,Cu2+,Zn2+,Mg2+ and Mn2+ reduced the quenching constants of the flavonoids for HSA by 14.6% to 60.7% , 28% to 67.9%,3.5% to 59.4%, 23.2% to 63.7% and 14% to 65%, respectively. The affinities of flavone, genistein and kaempferol for HSA decreased about 10.84%, 10.05%and 3.56% in the presence of Pb2+, respectively. Cu2+ decreased the affinities of flavone, genistein and kaempferol for HSA about 14.04%, 5.14%and 8.89%, respectively. Zn2+ decreased the affinities of flavone, genistein and kaempferol for HSA about 3.79%, 0.55% and 3.58%, respectively. Mg2+ decreased the affinities of flavone, genistein and kaempferol for HSA about 16.94%, 2.94%and 7.04%, respectively. Mn2+ decreased the affinities of flavone, genistein and kaempferol for HSA about 14.24%, 3.66% and 4.78%, respectively