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Showing papers in "Studies in natural products chemistry in 2008"


Book ChapterDOI
TL;DR: The network diagrams illustrating the relationships between glycoside structural elements and functional components (partial activities) as well as with general glycosid activity are shown to be useful for non-quantative predication of biological activity.
Abstract: The holothuroid triterpene glycosides have strong membranolytic action against cellular and model membranes containing Δ5-sterols as result of the formation of single-ion channels and more large pores that is the basis of hemolytic, antifungal, antitumor cytotoxic activities of these compounds. The binding presence of an 18(20)-lactone, and at any rate of one oxygen functional group near it for compounds with 9(11)-double bonds in lanostane aglycon moiety, is very important for the membranotropic action of these substances. A linear tetrasaccharide fragment in the carbohydrate chain is also essential for membranolytic action. A sulfate group at C-4 of the first xylose residue increases the effect against membranes. The absence of a sulfate group at C-4 of the xylose residue in biosides decreases the activities more than one order of magnitude. The presence of a sulfate at C-4 of the first xylose of branched pentaosides having 3-O-methyl group at a terminal monosaccharide increases activity but the same sulfate decreases the activity of branched pentaosides having terminal glucose residues. Sulfate groups attached to a C-6 position of terminal glucose and 3-O-methylglucose residues greatly decrease activity. Some glycosides may inhibit chemokine receptor subtype 5 (CCR 5). This activity is correlated with toxicity. Some glycosides possess immunostimulatory action in subtoxic doses. The most effective immunostimulants are monosulfated glycosides but di- and trisulfated are immunosuppressors. The network diagrams illustrating the relationships between glycoside structural elements and functional components (partial activities) as well as with general glycoside activity are shown to be useful for non-quantative predication of biological activity. The glycosides regulate of oocyte maturation in the sea cucumbers to synchronize maturation processes. This role is caused by the modifying action of the glycosides on the membranes of holothuroid eggs. The absence or very low concentration of Δ5-sterols in oocyte membranes suggests another nature of the modifying action in comparison with that against membranes containing Δ5-sterols. Holothuroid glycosides have defensive function against predators.

103 citations


Book ChapterDOI
TL;DR: Stilbenoids are formed by a particular branch of the flavonoid biosynthetic pathway and are of special interest to natural product researchers for their roles in plant resistance to fungal pathogens and their biological effects as discussed by the authors.
Abstract: Stilbenoids are formed by a particular branch of the flavonoid biosynthetic pathway. They are of special interest to natural product researchers for their roles in plant resistance to fungal pathogens and their biological effects. This review in the volume of Bioactive Natural Products provides a comprehensive account of the occurrence, chemistry, biological roles and activities of the stilbenoids. Nearly 800 stilbenoids, isolated from natural sources in the recent 12 years, are grouped into structural types and discussed in terms of their reported pharmacological activity. The major groups of stilbenoids which are discussed in detail include stilbenes, bibenzyls, bisbibenzyls, phenanthrenoids, stilbene oligomers etc. Detailed tables and figures list the occurrence of stilbenoids in major plant species, and methods used for extracting and analyzing stilbenoids are discussed. Biosynthetic pathways and chemical synthesis are reviewed and the biological activities of stilbenoids are also addressed. The coverage of the new structures is from 1994 to 2006.

75 citations


Book ChapterDOI
TL;DR: The functional roles of hyaluronan in living organisms, detection methods of HA degradation and of the resulting fragmentation products, as well as the involvement of HA in various pathologies and inflammatory processes are reviewed.
Abstract: Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disaccharide units containing N-acetyl- d -glucosamine and glucuronic acid. Its molecular mass can vary between 2 x 105 and 10 x 106 Da and its physiological properties are strongly influenced by its polymeric and polyelectrolyte character, as well by the viscous nature of its solutions. HA is abundantly present in almost all biological fluids and tissues. For experimental purposes, commercial HA samples are mostly of bacterial origin (grampositive streptococci) or isolated from rooster combs, while in the human organism it is distributed in the skin, vitreous humor of the eye, umbilical cords, cartilage, and synovial fluid. In the latter, HA serves to maintain its viscoelastic properties required for lubrication of the joint. When hyaluronan is degraded by the action of free radicals or certain enzymes, synovial fluid loses its lubricating properties, which leads to increased wear of the joint and results in arthritic pain. HA is also used as a diagnostic marker for many diseases including cancer, rheumatoid arthritis, and liver pathologies. It is widely used for supplementation of impaired synovial fluid in arthritic patients by means of intra-articular injections, as well as during certain ophthalmological and otological surgeries. The observed reduction of the molecular mass of HA in the synovial fluid of patients suffering from rheumatic diseases led to in vitro studies of HA degradation by reactive oxidative species. In this paper, the functional roles of hyaluronan in living organisms, detection methods of HA degradation and of the resulting fragmentation products (e.g. viscometry, HPLC, mass spectrometry, NMR spectroscopy, light scattering, rheology, etc.), as well as the involvement of HA in various pathologies and inflammatory processes are reviewed. Finally, some important medical applications of HA will also be described.

46 citations


Book ChapterDOI
TL;DR: It is indicated that medicinal plants offer significant potential for the development of novel antibacterial therapies and adjunct treatments (i.e. MDR pump inhibitors).
Abstract: For thousands of years medicinal plants have played a significant role in the treatment of a wide range of medical conditions, including infectious diseases. Some naturally occurring chemical compounds serve as models for a large percentage clinically proven drugs, and many are now being re-assessed as antimicrobial agents. The primary reason for this renaissance is the fact that infectious disease remains a significant cause of morbidity and mortality worldwide, accounting for approximately 50% of all deaths in tropical countries and as much as 20% of deaths in the Americas. Despite the significant progress made in microbiology and the control of microorganisms, sporadic incidents of epidemics due to drug resistant microorganisms and previously unknown disease-causing microbes pose an enormous threat to global public health. These negative health trends call for a global initiative for the development of new strategies for the prevention and treatment of infectious disease, including natural products. Literally thousands of plant species have been tested against hundreds of bacterial strains in vitro, and many medicinal plants are active against a wide range of gram-positive and gram-negative bacteria. However, very few of these medicinal plant extracts have been tested in animal or human studies to determine safety and efficacy. This review focuses on the medicinal plants and phytochemical for which there is significant published in vitro, in vivo and clinical data available. The examples provided in this review such as St. John's wort, tree tea oil, and green tea demonstrate that even commonly used plant extracts may offer prospective new treatment of bacterial infections, including multi-drug resistant bacteria. One interesting example is St. John's wort (Hypericum perforatum) and its active constituent hyperforin, both of which have significant activity against MRSA in microgram concentrations. This antibacterial discovery was based on the ethnomedical use of St. John's wort to treat skin infections and wounds. Review of the published data indicates that medicinal plants offer significant potential for the development of novel antibacterial therapies and adjunct treatments (i.e. MDR pump inhibitors). However, new investigations should employ modern methodology, including using nationally recognized protocols and standards for microbial testing, the generation of minimum inhibitory concentrations, as well as standardization of the quality of plant materials used for testing.

42 citations


Book ChapterDOI
TL;DR: In this paper, a review covers the structures of compounds with anti-osteoporotic activity isolated from plants and are organized according to chemical classes; a total of 104 structures have been reviewed from 79 references found in the literature up to December 2005.
Abstract: This review covers the structures of compounds with antiosteoporotic activity isolated from plants and are organized according to chemical classes. A total of 104 structures have been reviewed from 79 references found in the literature up to December 2005.

39 citations


Book ChapterDOI
TL;DR: The past, present and future of medicinal plants of the Anthemideae tribe of the Asteraceae are analyzed, both as potential antimicrobial crude drugs as well as a source for natural compounds that act as new anti-infectious agents.
Abstract: Infectious diseases account for one third of all deaths worldwide. The spread of multidrug-resistant strains of microbes makes it necessary to discover new classes of antimicrobials and compounds that inhibit these resistance mechanisms. In the past few decades, the search for new anti-infective agents has occupied many research groups in the field of ethnopharmacology. Many focus on determining the antimicrobial activity of plant extracts found in folk medicine, essential oils or isolated compounds. The Anthemideae tribe of the Asteraceae comprises a large number of species that have been and are still used as medicinal plants, particularly in folk medicine. In the present review, we analyze the past, present and future of medicinal plants of the Anthemideae tribe, both as potential antimicrobial crude drugs as well as a source for natural compounds that act as new anti-infectious agents.

35 citations


Book ChapterDOI
TL;DR: The antibacterial activity of the roots of S. jaminiana while the antioxidant activity have been established for the seven diterpenoids isolated from S. barrelieri.
Abstract: More than 550 diterpenoids have been isolated from Salvia species widely distributed in Mexico, Turkey, Spain and China. 23 species grow in Algeria, five of them are endemic. We've recently isolated five abietane diterpenoids from each of the endemic species S. jaminiana and S. verbenaca subsp. clandestina and seven diterpenoids, from which three are new, from the endemic species S. barrelieri. We've recently reported the antibacterial activity of the roots of S. jaminiana while the antioxidant activity have been established for the seven diterpenoids isolated from S. barrelieri. Salvia diterpenoids could be divided into 2 categories. The first category includes one monocyclic and bicyclic diterpenoids containing labdanes, clerodanes, neoclerodanes, seco-clerodanes and other rearranged clerodanes. The second category concerns tricyclic and tetracyclic diterpenes represented by pimaranes and abietanes including quinone abietanes, nor-abietanes, rearranged nor-abietanes, dinor-abietanes, seco-abietanes, tanshinones and other particular rearranged abietanes. A great number of the described Salvia diterpenoids exhibited interesting biological activities e.g anti-tuberculous, antitumour, antimicrobial, antibacterial, antileishmanial and antispasmolytic.

35 citations


Book ChapterDOI
TL;DR: The purpose of this communication is to review the structural characteristics and biological properties of the saponins isolated from starfishes and sea cucumbers in the last five years, focusing on the structural elucidation and evaluation of antifungal, cytotoxic and antiviral properties of some examples of the author's laboratory isolated near the Patagonian shore and Antarctica.
Abstract: The classes Asteroidea (starfishes) and Holothuroidea (sea cucumbers) belonging to the phylum Echinodermata are characterized by their content in toxic saponins. Asterosaponins from starfishes are sulfated steroidal glycosides whereas holothurins from sea cucumbers are triterpenoid glycosides with sulfate groups attached to the monosaccharide residues in sixty percent of the saponins isolated so far. Starfishes also contain steroidal mono- and diglycosides which occur as complex mixtures with asterosaponins. Due to their toxicity and membranotropic action, these polar compounds have attracted the attention of chemists and pharmacologists and a wide spectrum of biological activities has been found for these saponins. The purpose of this communication is to review the structural characteristics and biological properties of the saponins isolated from starfishes and sea cucumbers in the last five years, focusing on the structural elucidation and evaluation of antifungal, cytotoxic and antiviral properties of some examples of the author's laboratory isolated from starfishes and sea cucumbers collected near the Patagonian shore and Antarctica.

34 citations


Book ChapterDOI
TL;DR: It is shown that, in spite of the great biological and cultural potential in Brazil, there is, even today, no phytomedicines originating from this flora, as an alternative to allopathic anxiolytics and hypnotics prescribed by psychiatry.
Abstract: This study shows that, in spite of the great biological and cultural potential in Brazil, there is, even today, no phytomedicines originating from this flora, as an alternative to allopathic anxiolytics and hypnotics prescribed by psychiatry. Thirty-nine plants with potential anxiolytic effects and 28 hypnotics were indicated in the course of ethnopharmacological surveys carried out with Afro-Brazilians and/or Quilombolas, the Caboclo population (river-dwellers), and Indians in Brazil. Practically no pharmacological studies have been found in the scientific literature as evidence of their popular use. From the phytochemical point of view, it is of interest to observe that flavonoids, essential oils, phenolic acids, and alkaloids are the chemical constituents predominantly present in these species, both in those indicated as anxiolytic, and the hypnotic.

33 citations


Book ChapterDOI
TL;DR: In this paper, Matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) techniques have been used for peptide identification and determination of post-translational modifications.
Abstract: Bioactive natural peptides are ubiquitous in all life kingdoms. They are often characterized by short amino acid sequences and they are found either free or encrypted in proteins thus requiring enzymatic hydrolysis for their release. Matrix-assisted laser desorption/ionization (MALDI) MS and electrospray ionization (ESI) MS techniques have been used for peptide identification and determination of post-translational modifications, directly from body fluids, organs, tissue samples or single-cells. Peptide structures have also been studied by CD and NMR spectroscopy. Antimicrobial peptides (AMPs) synthesized by microorganisms and multicellular organisms can have linear, cyclic or open-ended cyclic structures with one or more disulfide bridges. They exhibit α-helical conformations, amphipathic β-hairpin-like β-sheet, β-sheet and α-helix/β-sheet mixed folds. Some of them, in addition to containing hydrophobic amino acid residues, are rich in proline, histidine, arginine or lysine. AMPs exhibit two main modes of action, one involving an intracellular target, and another the interaction with the cytoplasmic membrane from microorganisms. Membrane-active peptides that include hormones, signal sequences and lytic agents, interact electrostatically with the cellular external membrane and eventually partition into the hydrophobic lipid bilayer where they express their activity. Counterparts of several human endogenous peptides of pharmacological and immunobiological importance are found also in other animal species and they have become the lead for development of new drugs. An increasing number of them display direct or immune-stimulated antitumor activities. Multifunctional peptides have also been recognized in food sources. Owing to the wide reactivity of endogenous peptides generated in cells, appropriate oligopeptide restricted peptidases either give rise to bioactive shorter peptides or contribute to the complete degradation of oligopeptides.

30 citations


Book ChapterDOI
TL;DR: The present review describes the chemistry, biological activities and pharmacology of natural cyclic lipopeptides, which consist of acyl side chains and peptides of various kinds, some including unusual amino acids.
Abstract: Numerous natural products have been discovered, mainly from microorganisms, algae and plants, that often exhibit interesting and useful biological activities. Of these, cyclic lipopeptide antibiotics form the biggest group and provide several clinically important drugs. Cyclic lipopeptide antibiotics consist of acyl side chains and peptides of various kinds, some including unusual amino acids. These characteristics confer a wide variety of biological activities and structural diversity on cyclic lipopeptide antibiotics. It is also interesting and noteworthy that the structural similarities of cyclic lipopeptides do not always reflect any similarity in their biological activities. The present review describes the chemistry, biological activities and pharmacology of natural cyclic lipopeptides.

Book ChapterDOI
TL;DR: This review focuses particularly on organic syntheses by which selective polymerization of 3-alkylpyridinium polymers may be achieved and the biological activities and potential use of alkylpyrid iniumPolymers and the role played by mass spectrometry is reviewed.
Abstract: During the last 30 years, a number of simple 3-alkylpyridine and 3-alkylpyridinium (3-AP) compounds have been isolated from marine sponges belonging to the order Haplosclerida, suggesting these compounds as chemical markers for systematic determination of haplosclerid sponges. They were isolated from haplosclerid sponges either as (i) monomers differing in the length, saturation, branching and termination of the alkyl chains, (ii) cyclic or linear oligomers, or (iii) a mixture of high-molecular weight polymers. What the biosynthetic pathways are in marine sponges, and how these compounds can be made by organic synthesis is also an interesting question addressed in our review. In this regard we focus particularly on organic syntheses by which selective polymerization of 3-alkylpyridinium polymers may be achieved. Structural investigation of alkylpyridinium compounds and the role played by mass spectrometry has also been reviewed. In spite of their relatively simple chemical structure, all these compounds exert a broad spectrum of biological activities. More than 40 monomeric 3-AP compounds have been isolated from marine sponges and the majority bear a nitrogenous functionality at the end of the alkyl chain. Almost all reported 3-AP monomers exert moderate cytotoxicity, in the concentration range of a few micrograms per millilitre, against certain transformed cell lines. An example of 3-alkylpyridines is niphatyne A, from the marine sponge of the genus Niphates which exhibits an IC 50 of 0.5 μg/mL against several transformed cell lines. The majority of 3-AP dimers and trimers were isolated from haplosclerid sponges in cyclic forms. Haliclamines are a typical representative of this group. They inhibit the division of fertilized sea urchin eggs as well as the growth of several transformed cell lines. On the other hand cyclostellettamines are typical example of cyclic alkylpyridinium dimers that modulate muscarinic receptors. Recently an increasing number of polymeric alkylpyridinium compounds have been isolated from haplosclerid sponges. Halitoxins, amphitoxins and alkylpyridinium salts from Mediterranean sponge Reniera sarai are the most studied. The latter exhibit a plethora of interesting biological activities. For instance, they are able to make pores in membranes through which DNA can be transfected into the cell, show selective cytotoxic activity against certain human cancer cells and possess non-toxic inhibitory antifouling properties against larvae of several important fouling organisms. The biological activities and potential use of alkylpyridinium polymers are discussed.

Book ChapterDOI
TL;DR: The pyroglutamate was isolated from the Basidiomycete fungus Agaricus blazei as an anti-angiogenic substance, and pyrogLutamate inhibited the tumor growth and lung metastasis in tumor-bearing mice.
Abstract: Although it has been recently thought that a number of medicinal plants and foodstuffs have antitumor and antimetastatic activities, the basis for this hearsay is unclear. Therefore, to clarify whether natural products have preventive effects on tumors growth and tumor metastasis, it has been using some biochemical and pharmacological approaches to examine the natural products isolated from various medicinal plants and food stuffs. In the present review, the antitumor and antimetastatic actions of various compounds isolated from some medicinal plants and foodstuffs were clarified by the analysis of biochemical and pharmacological approaches. The various foodstuffs such as Royal Jelly, tuna oil (main compound, DHA), EPA derivatives such as EPA dimer and low-molecular water-soluble chitosan inhibited the tumor growth and/or metastasis in the liver or lung, through the inhibition of tumor-induced angiogenesis and/or the activation of immune function. Chalcone derivatives such as xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots also inhibited the tumor growth and liver metastasis in tumor-bearing mice, through the inhibition of tumor-induced neovascularization and the stimulation of immune functions. Moreover, the pyroglutamate was isolated from the Basidiomycete fungus Agaricus blazei as an anti-angiogenic substance, and pyroglutamate inhibited the tumor growth and lung metastasis in tumor-bearing mice.

Book ChapterDOI
TL;DR: An overview of recent experimental approaches and obtained results on the genes and corresponding proteins involved in cytokinin biosynthesis, modification, degradation and signal transduction is presented.
Abstract: Cytokinins are plant hormones that contribute to the regulation of a variety of developmental processes including apical dominance, flower and fruit development, leaf senescence, and seed germination. Numerous cytokinins have been characterized in different plant species. Differences among cytokinins are related predominantly to structural features, including the side chain that is attached to an adenine moiety, conjugation with sugars and phosphorylation. These hormones bind to cell surface receptors and initiate a signal transduction cascade that leads to activation of genes involved in tissue development. Over the past decade, many genes have been identified that affect cytokinin synthesis, transport, metabolism, and their function in growth regulation. In Arabidopsis , it appears that a gene family of over 20 members controls these processes. This paper presents an overview of recent experimental approaches and obtained results on the genes and corresponding proteins involved in cytokinin biosynthesis, modification, degradation and signal transduction.

Book ChapterDOI
TL;DR: The presence of the isoquinuclidine (2-azabicyclo[222] octane) ring system in natural products displaying interesting pharmacological properties (such as ibogaine and dioscorine) has interested chemists and medicinal chemists for decades as mentioned in this paper.
Abstract: The presence of the isoquinuclidine (2-azabicyclo[222]octane) ring system in natural products displaying interesting pharmacological properties (such as ibogaine and dioscorine) has interested chemists and medicinal chemists for decades This ring system may be viewed as a semi-rigid boat form of the piperidine ring and, when properly substituted, as a scaffold for rigid analogs of biologically active ethanolamines and propanolamines Many pharmacologically active compounds based on the isoquinuclidine system have been synthesized utilizing standard or combinatorial chemistry techniques and diversity oriented synthetic routes have led to interesting derivatives which will be reviewed here

Book ChapterDOI
TL;DR: This review examines advances in alpine plants in the last ten years with reference to early work as required for better understanding, with emphasis on some of the chemical processes related to acclimation and adaptation of plant species in high elevations.
Abstract: As a group, alpine plants stand among the least well studied organisms of terrestrial ecosystems today. Misconceptions about poor biodiversity, small number of individuals per species, reduced surface, inaccessibility, and relative simplicity of these habitats have sent most plant scientists elsewhere in search for more inviting places to do research. However, the few that decided to explore the riches of the alpine zone have found an intriguing range of peculiar qualities that make the high elevation plant community among the most interesting examples of well adapted terrestrial life to extreme conditions. High elevation is characterized by severe and frequently life-threatening abiotic conditions that change dramatically not only following the winter-summer yearly cycles but also even changing on a daily basis as in high tropical ranges. Plants, nevertheless, are capable of growing successfully at altitudes surpassing 5000 m thanks to highly specialized physiological processes that affect the chemical response of the plant, from the synthesis of special lipids that modify cell membranes for flexibility and water permeability, to anti-freeze carbohydrates, ultraviolet filters, potent antioxidants and free radical quenchers not seen in low altitude plants. Their biochemical machinery has been able to dodge the aggressive climatic forces that challenge the fundamental mechanisms of life by way of new biosynthetic twists leading to new molecular skeletons which are absent in their relatives of lower elevations. It is very unfortunate, however, that these exquisite habitats are being modified by the effects of global warming at a pace that we only begin to understand, which tends to displace upwards the vegetational belts that build themselves around mountain flanks and summits. Eventually, the species occupying the upper tiers of each mountain range will disappear under the push of other plants from beneath which are better adapted to warmer climates and less stringent conditions. With their demise their secrets will also vanish for the foreseeable future, secrets that are essential keys to life that allow them to survive very low temperatures and excess ultraviolet solar radiation, genetic traits that will be necessary to retrieve and insert in food plants if we are to survive the coming planetary crisis. This review examines advances in alpine plants in the last ten years with reference to early work as required for better understanding, with emphasis on some of the chemical processes related to acclimation and adaptation of plant species in high elevations. However, phytochemistry cannot and should not be an isolated endeavor when it comes to highly specialized organisms of endemic character such as these, and consideration of the ecological entourage that surrounds these species is a necessity if we want to understand the inner workings of these habitats and not solely pursue new molecular structures, pharmaceuticals and other useful materials that these plants conceal. It is the purpose of this chapter to provide such an integrated view.

Book ChapterDOI
TL;DR: Micropropagation methods for Cephaelis ipecacuanha were established and these methods enabled much more efficient propagation of plants than the conventional methods using seedling or layering, and the production of important pharmaceuticals of plant origin by these cultures was successfully demonstrated.
Abstract: Plant tissue culture studies were carried out for the preservation of medicinal plant resources and efficient production of pharmaceutically important secondary metabolites. Micropropagation methods for Cephaelis ipecacuanha were established and these methods enabled much more efficient propagation of plants than the conventional methods using seedling or layering. The C. ipecacuanha plants propagated through tissue culture grew uniformly in the field and they constituted relatively high alkaloid contents compared to the plants grown from seedling. Adventitious root cultures of Cephaelis ipecacuanha and Duboisia myoporoides-D. leichhardtii hybrid were grown. These root cultures produced sufficient amount of pharmaceutically important alkaloids (emetine and cephaeline in C. ipecacuanha ; scopolamine and hyoscyamine in Duboisia hybrid ) in MS liquid medium supplemented with IAA chloro-derivatives. The alkaloid yields from cultured roots of C. ipecacuanha , grown for seven weeks in 50 ml MS liquid medium containing 0.01 mg/l 5,6-Cl 2 -IAA are comparable to those from roots of a one-year-old plant cultivated in a greenhouse. Transformed cultures of Duboisia myoporoides-D. leichhardtii hybrid, Atropa belladonna , Cephaelis ipecacuanha , Digitalis lanata and Papaver somniferum have been established by infection with Agrobacterium rhizogenes , and the production of important pharmaceuticals of plant origin by these cultures was successfully demonstrated. In the case of Digitalis lanata hairy roots, it was elucidated that the greening of the roots under the light stimulated cardenolides formation. Transgenic plants were successfully obtained from the transformed cultures of Atropa belladonna , Cephaelis ipecacuanha and Papaver somniferum , in line with the molecular breeding of these plants using Agrobacterium rhizogenes . Furthermore, the production of low morphine Papaver somniferum plants, which mainly contain codeine, was first achieved by transformation of Agrobacterium rhizogenes .

Book ChapterDOI
TL;DR: This review deals with the application of recombinant DNA technology to investigate and tailor plant secondary metabolism as a tool for the control of the biosynthesis and accumulation of plant natural products.
Abstract: This review deals with the application of recombinant DNA technology to investigate and tailor plant secondary metabolism as a tool for the control of the biosynthesis and accumulation of plant natural products. Firstly, it presents the different plant transformation technologies, followed by the description of the various strategies implemented for the genetic modification of metabolic pathways. Furthermore, a review of the modification of three metabolic pathways, i. e. tropane alkaloid, fatty acid and terpenoid biosynthetic routes has also been attempted. Finally, under future perspectives several views on how the technology might progress are outlined, as well as presenting the potential different approaches which might be devised in the future for the genetic engineering of metabolic networks.

Book ChapterDOI
TL;DR: The thermodynamic and thermotropic properties of model lipidic membranes, their formation to lipidic drug carriers, their encapsulation efficiency and their physicochemical stability are underlined.
Abstract: The lipids are a wide and heterogeneous class of natural products. They are considered as essential biomolecules for the structure and function in living cells. The classification of lipids is not so simple. Many systems have been proposed in the recent literature in order to classify the lipids. This review article deals with the structure and classification of the main lipid classes that are taking part in the membrane structure, [glycerolipids (i.e. glycerophospholipids and glyceroglycolipids), sphingolipids (i.e. shingophospholipids and shingoglycolipids), sterols], their biological role and their applications as drug carriers. Glycerolipids and sphingolipids have a hydrophilic polar group and a hydrophobic carbon chain, they are characterized as amphiphilic and they can form lipid bilayers in water. The presence of sterols in membrane can influence their thermotropic behavior, resulting in the stabilization of the bilayer. This report underlines the thermodynamic and thermotropic properties of model lipidic membranes, their formation to lipidic drug carriers, their encapsulation efficiency and their physicochemical stability. Additionally, paradigms concerning bioactive natural products (i.e. diterpenes and flavonoids) encapsulating into lipidic drug carriers such as liposomes, are underlined.

Book ChapterDOI
TL;DR: Evaluation of (+)-( S )-tylophorine and its analogs in the National Cancer Institute's antitumor screen showed a uniform and potent inhibitory effect on the cell growth against all 60 cancer cell lines, with notable selectivity toward several refractory cell lines.
Abstract: Tylophorine (1) and related phenanthroindolizidine alkaloids, also known as Tyophora alkaloids, have been isolated principally from plants of the family Asclepiadaceae , including members of the genus Tylophora . Because of their profound cytotoxicity, these compounds have been targets of synthetic modification. Evaluation of (+)-( S )-tylophorine and its analogs in the National Cancer Institute's antitumor screen showed a uniform and potent inhibitory effect on the cell growth (G1 50 ≅ 10 -8 M) against all 60 cancer cell lines, with notable selectivity toward several refractory cell lines, including melanoma and lung tumor cell lines. However, to date, this compound class has not been successfully developed for clinical use in cancer due to the CNS toxicity of tylocrebrine reported in 1966. Most recently, tylophorine analogs have shown significant inhibitory effects on NF-κB mediated transcription, a unique mode of antitumor action that differs from those of the current known antitumor drugs. This recent discovery points to a great potential for developing tylophorine derivatives as a new antitumor drug class. Motivation is high in many research laboratories and a renewed and expedited exploration of tylophora alkaloids is anticipated. Therefore, this article contains a comprehensive review of isolation, total synthesis, antitumor activity and structure-activity relationship (SAR) correlations of tylophorine-related alkaloids.

Book ChapterDOI
TL;DR: This review, the emphasis is placed on new compounds with antitumor, enzyme inhibitors, antivirus, and other bioactive metabolites from fungi, bacteria, actinomycetes, and cyanobacteria reported between 2000 and 2005.
Abstract: Diverse arrays of new bioactive secondary metabolites have been isolated from marine microorganisms; and the number of publications in this area has greatly increased in recent years. In this review, the emphasis is placed on new compounds with antitumor, enzyme inhibitors, antivirus, and other bioactive metabolites from fungi, bacteria, actinomycetes, and cyanobacteria reported between 2000 and 2005. Supply is a major limitation in the development of marine bioproducts, and the methods for supplying these products are important. So in this review, the secondary major point is placed on the chemical synthetic studies. References of 390 structures and 263 citations are overall presented in this review.

Book ChapterDOI
TL;DR: This review presents an account of some research directed toward the discovery of new antiviral agents from marine sources, including polysaccharides, terpenoids, steroids, alkaloids and peptides that potentially inhibit both RNA and DNA viruses.
Abstract: The oceans are unique resources that provide a diverse array of natural products, primarily from invertebrates such as sponges, tunicates, bryozoans and molluscs and from marine bacteria and cyanobacteria. Pharmacologic research with marine chemicals continue to contribute potentially novel chemical leads in the ongoing global search for therapeutic agents in the treatment of multiple diverse categories. As infectious diseases evolve and develop resistance to existing pharmaceuticals, the marine environment provides novel leads against fungal, parasitic, bacterial and viral diseases. Limitations in our current antiviral treatment options and the continuing emergence of new pathogenic viruses have contributed to a growing need for new and effective chemotherapeutic agents to treat viral diseases. The search for potent antiviral agents is urgent in view of the dramatic situation of the global human immunodeficiency virus (HIV) epidemic, a possible spread of avian influenza and of other viral diseases. Effective antiviral therapeutics are not available, and the presently approved therapy for HIV has been recognized to be toxic, unable to eradicate the causative virus, and to induce severe drug resistance. The marine environment provides a rich source of chemical diversity for the screening and identification of new compounds with desirable antiviral properties. Antiviral testing has revealed numerous compounds from structural classes including polysaccharides, terpenoids, steroids, alkaloids and peptides that potentially inhibit both RNA and DNA viruses. This review presents an account of some research directed toward the discovery of new antiviral agents from marine sources.

Book ChapterDOI
TL;DR: The relative molecular simplicity of combretastatins, associated with their important anticancer properties, offers promises for the rational design of new chemotherapeutic agents.
Abstract: Natural compounds play a key role in the cancer prevention and treatment. Among them stilbene-based compounds are widely distributed in nature and show a wide range of biological activities. Certain poly-hydroxylated cis -stilbenes and their analogues bind in the colchicin site of tubulin and inhibit cancer cell proliferation. Up-to-now the most promising of these compounds is combretastatin A-4 ( cis -3,4,4',5tetramethoxy-3'-hydroxy stilbene ) which has been shown to cause mitotic arrest in a variety of cancer cell lines, including multi-drug-resistant ones, and has also demonstrated cancer antiangiogenetic properties. The relative molecular simplicity of combretastatins , associated with their important anticancer properties, offers promises for the rational design of new chemotherapeutic agents. In this context, many efforts have been devoted to the detailed study of the structure-activity relationship of various substituted stilbenes as well as soluble prodrugs; to the development of new synthetic methods; and to the design of analogues with improved activities.

Book ChapterDOI
TL;DR: Recent work isolated a variety of marine natural products from the Okinawan marine invertebrates by using the sea urchin egg assay, and the isolation, structure determination and activities of chlorinated macrolides, sesterterpenic acids, a bromotyrosine derivative, acetogenin derived endoperoxides, diterpene alkaloids and spiro-sesquiterpenes are presented.
Abstract: Marine invertebrates such as ascidians, sponges and others are a prolific source of bioactive secondary metabolites. We have isolated a variety of marine natural products from the Okinawan marine invertebrates by using the sea urchin egg assay. Our recent work, the isolation, structure determination and activities of chlorinated macrolides, sesterterpenic acids, a bromotyrosine derivative, acetogenin derived endoperoxides, diterpene alkaloids, sesquiterpene quinones and spiro-sesquiterpenes, is presented in this article. The syntheses of these metabolites are also described.

Book ChapterDOI
TL;DR: Thyrsiferol was originally isolated off the coast of New Zealand from a marine red algae of the genus Laurencia and several analogues having similar structural features have been identified and their biological properties investigated and identified.
Abstract: Marine natural products have played an important role in the discovery of novel biologically active compounds. Thyrsiferol was originally isolated off the coast of New Zealand from a marine red algae of the genus Laurencia. Several analogues having similar structural features have been identified and their biological properties investigated and identified. The array of activities is significant and includes: cytotoxic, anti-viral, and anti-tumor activity, the specific inhibition of protein serine/threonine phosphatase 2A, and apoptotic cell death in human leukemic T- and B-cell lines. Therefore, it is of interest to design and develop methods that would make these compounds accessible in the laboratory through synthetic organic chemistry. This review will discuss the biological properties and synthetic endeavors that have been used to access thyrsiferol and related analogues.

Book ChapterDOI
TL;DR: In this paper, three synthetic approaches to (+)-biotin have been investigated to develop an efficient synthetic method using L-cysteine and thiolactone as a starting material and a key intermediate, respectively.
Abstract: The course of our investigation to develop an industrially viable total synthesis of (+)-biotin is described. Three synthetic approaches to (+)-biotin have been investigated to develop an efficient synthetic method using L-cysteine and thiolactone as a starting material and a key intermediate, respectively. Short steps, high yield and ease of operation of the approach would permit the hitherto most efficient access to (+)-biotin.

Book ChapterDOI
TL;DR: In the course of bioorganic studies on the phytotoxins isolated from culture filtrates of phytopathogenic fungi, we happen to use the Diels-Alder reaction in order to eliminate a byproduct.
Abstract: In the course of bioorganic studies on the phytotoxins isolated from culture filtrates of phytopathogenic fungi, we happen to use the Diels-Alder reaction in order to eliminate a by-product. This procedure was motivated to develop the retro Diels-Alder reactions, which have been applied to the syntheses of bioactive natural products. At the same time, we isolated several phytotoxins, which have incidentally the Diels-Alder type structure. Among these phytotoxins, we succeeded to purify two Diels-Alderases, solanapyrone synthase and macrophomate synthase. Recently the crystal structure of later enzyme made possible to reveal the mechanistic process from 2-pyrone to macrophomic acid. Lovastatin nonaketide synthase which catalyzes intramolecular Diels-Alder reaction in the biosynthesis of lovastatin, cholesterol-lowering drug, was confirmed. Other natural Diels-Alder adducts are discussed briefly and utilities of the Diels-Alderases are commented.

Book ChapterDOI
TL;DR: In the synthesis of relevant organic compounds such as natural products and analogues, the proportion of the number of steps coupled with the increase of complexity is now a universal paradigm to ascertain the quality and efficiency of a process.
Abstract: In the synthesis of relevant organic compounds such as natural products and analogues, the proportion of the number of steps coupled with the increase of complexity is now a universal paradigm to ascertain the quality and efficiency of a process. Alongwith providing accessibility to a multitude of diversified classes of natural products such as alkaloids, terpenoids, steroids and others, these criteria have been addressed by us via the application of domino processes. The acid-catalyzed intermolecular cyclization has been used as a viable synthetic tool for the stereospecific formation of different classes of polycyclic natural products.

Book ChapterDOI
TL;DR: Various aspects of the concept, classification, identification, biosynthesis, chemistry and biological properties of pheromones, and the available evidence relating to the vomeronasal organ (VN0), human phermones and their possible role in human behavior are described.
Abstract: This work describes various aspects of the concept, classification, identification, biosynthesis, chemistry and biological properties of pheromones In addition, the available evidence relating to the vomeronasal organ (VN0), human pheromones and their possible role in human behavior is summarized The latest works on the synthesis of pheromones with relevant activities are also included