Showing papers in "Studies in natural products chemistry in 2003"

Plant Polyphenols: Structure, Occurrence and Bioactivity

Abstract: Main dietary plant polyphenols are grouped into structural types and their occurrence in most common foods and beverages is briefly described. The major groups of plant polyphenols which are examined include flavonols, flavones, flavanones, isoflavones, anthocyanins, proanthocyanidins and flavanols. The current evidence on the absorption and the metabolism of each group is discussed. The biochemical and pharmacological activities of plant polyphenols are summarized, including antioxidant and anti-radical activity, chelation of metal ions, modulation of some enzymes activity, anticarcinogenic, antiatherosclerotic, anti-inflammatory, spasmolytic, hepatoprotective, antiviral, antimicrobial and oestrogenic activity, and inhibition of histamine release. An overview on the epidemiological evidence linking the intake of plant polyphenols and diminished risk of chronic diseases is also included.

Natural Bridged Biaryls with Axial Chirality and Antimitotic Properties

Abstract: Numerous molecules containing a biaryl unit have been found in Nature. Many of them exhibit a variety of biological actions. In this review, we will focus only on natural bridged biaryls that possess axial chirality and exhibit antimitotic activities. Thus, we will first present the occurrence and structure of three families of natural compounds that display these particular structural and biological features: the allocolchicinoids, steganes and rhazinilam-type compounds. We will then describe the semi-synthetic and synthetic approaches to biaryls belonging to these three series. Their interaction with tubulin, a heterodimeric protein that is critical for the formation of microtubules and consequently of the mitotic spindle, will be discussed.

Potentially Cancer Chemopreventive And Anti-Inflammatory Terpenoids From Natural Sources

Abstract: Cancer chemoprevention by naturally occurring substances, especially by those occurring in vegetable foods and medicinal plants, seems to be a promising approach since various phytochemicals isolated from these sources have potent chemopreventive activity in animal experiments. Many phytochemicals have the advantage of being non-toxic. A number of terpenoids, which occur as secondary metabolites in all major groups of organisms, from fungi to humans, have been shown to possess chemopreventive activities in animal models. In a recent publication we have discussed the antitumor-promoting and anti-inflammatory activities of naturally occurring triterpenoids and sterols [1]. In this review article we describe the potentially chemopreventive and anti-inflammatory activities of terpenoids of the mono-, sesqui-, di-, sester-, and meroterpenoid classes, and of retinoids. Terpenoids are minor but ubiquitous components of our diet, and are considered relatively non-toxic to humans. These compounds, therefore, have the potential of being used as cancer chemopreventive agents.

Sulfur-Containing Natural Products from Marine Invertebrates

Abstract: An overview of sulfur-containing natural products isolated from the marine invertebrate phyla that are commonly studied by natural products chemists, is provided The material is arranged by phyla and sulfated compounds are included, except for the Echinodermata where sulfated saponins and steroids are specifically excluded A total of 638 compounds and 530 references are recorded The review covers the published literature up until the end of 2001 References to reported syntheses and comments on biological activities of metabolites are included

Polyhydroxy-P-Terphenyls and Related P-Terphenylquinones From Fungi: Overview and Biological Properties

Abstract: Natural occurrence of products with a p -terphenyl core is essentially restricted to fungi and lichens. Recently, an increasing number of metabolites based on the p -terphenyl nucleus and showing interesting biological properties or unusual structures has been reported. The literature on polyhydroxy- p -terphenyls and p -terphenylquinones isolated from 35 different fungal species (both from fungal cultures or from fruiting bodies of basidiomycetes) has been reviewed, and a total of 115 fungal metabolites are reported here, with emphasis on their biological properties. Some semisynthetic analogues or lichen metabolites are also included. An array of biological activity has been reported for these metabolites, and in particular for fully aromatic polyhydroxy- p -terphenyls, including cytotoxic activity against tumoral cells and other antiproliferative properties, antibacterial activity, antioxidant or radical scavenging activity, anti-inflammatory activity and other properties of biomedical or agronomical interest. Simple p -terphenyls with a tricyclic C-18 basic skeleton, including their acyclic O -alkyl or O -acyl derivatives are treated in Section 2. Those showing a polycyclic C-18 skeleton are discussed in Section 3, while Section 4 includes those possessing an alkylated skeleton (C-19 or more). The main biosynthetic pathways and synthetic methods for some of the cited metabolites are summarised in Sections 5 and 6, respectively. Globally considered, the data here reported confirm the important properties of this peculiar group of metabolites and open promising perspectives in the search for further bioactive polyhydroxy- p -terphenyls.

Biologically Active Triterpene Glycosides from Sea Cucumbers (Holothuroidea, Echinodermata)

Abstract: Sea cucumbers are characterized by their content in holothurins, triterpenoid glycosides that are responsible for the toxicity of these echinoderms. Nearly 100 holothurins isolated in the last twenty years are grouped into three main aglycone structural types: 3β-hydroxyholost-9(11)-ene, 3β-hydroxyholost-7-ene and non-holostane based aglycones. This communication offers a general view of the structural characteristics of these saponins and the spectral features in their 1 H-and 13 C-NMRand FAB-MS spectra. Recent advances in the unambiguous spectroscopic characterization of the triterpenoid skeleton, the substitution patterns and the complete structure of the oligosaccharide chain are discussed.

Generating and Screening a Natural Product Library for CYclooxygenase and Lipoxygenase Dual Inhibitors

Abstract: Natural products are a highly diversified structural pool for the discovery of potential drug leads. Recent technological developments in the fields of high throughput purification, LC/PDA/MS/MS/NMR for structural dereplication, and informatic databases have fundamentally changed the study of bioactive natural products and significantly accelerated the lead discovery process. This article summarizes the current state of parallel fractionation and purification technology for generating natural product fraction and compound libraries. Structural dereplication options using a combination of on-line and offline LC/PDA/MS/NMR techniques coupled with biological screening processes are reviewed. Adequate usage of structural, spectroscopic, and other databases with related physical and biological properties will also be discussed. The characteristics and advantages of a technology platform - Phytologix™ in generating and screening extract and fraction libraries will be detailed. Finally, this article will review recent publications on natural products with dual cyclooxygenase and lipoxygenase inhibitory activities and present the discovery and development of a novel anti-inflammatory ingredient - Univestin™ by screening a proprietary natural product library.

Protein and Non-Protein Protease Inhibitors from Plants

Abstract: Plants are consumed by bacteria, fungi and animals and utilization of plant proteins requires their hydrolysis, a process which is catalyzed by proteases Plants defend themselves against other organisms by elaborating physical and chemical defenses, the latter including protein and non-protein inhibitors of proteases Plant protease inhibitor proteins can be either constitutive or inducible as a result of wounding or pathogen invasion Proteases are classified into the aspartic proteases, cysteine proteases, metalloproteases and serine proteases on the basis of the involvement of aspartate, cysteine, metal ions and serine, respectively, in the catalytic mechanism Extracellular proteases are involved in digestion, blood clotting, inflammatory responses to invasion, and extracellular matrix digestion required for angiogenesis and tissue remodelling Intracellular proteolysis must be exquisitely regulated to avoid autolysis and intracellular proteases are involved in proprotein processing, lysosome- and proteasome-mediated protein destruction, cell division and apoptosis A large variety of plant protease inhibitor proteins and peptides have been resolved including aspartic protease inhibitor proteins, cysteine protease inhibitory phytocystatins, metallocarboxypeptidase inhibitor proteins and serine protease inhibitor proteins such as the Bowman-Birk, cereal bifunctional, Kunitz, potato type I, potato type II, mustard family, squash family, serpin and other protease inhibitors Plant protease inhibitor proteins have potential transgenic applications for crop plant defense A variety of non-protein protease inhibitors have also been resolved from plants Plant protease inhibitors have potential for pharmaceutical development especially in relation to Alzheimer’s disease, angiogenesis, cancer, inflammatory disease and viral and protozoal infection

Bioactive Tetramic Acid Metabolites

Abstract: Secondary metabolites containing the tetramic acid (2,4-pyrrolidine-2,4- dione) ring system have been known for almost half a century, and well before the parent system was synthesised. Although the first naturally occurring tetramic acids were identified because of their activity as antibiotics and/or mycotoxins, more recently tetramic acid-containing compounds have been found to display a remarkable diversity of biological activities. The often unusual and intricate substituents modifying the tetramic acid structural unit make the synthesis of these metabolites a challenging target. Recent studies has confirmed that these metabolites have a wide distribution and play a significant role in ecological interactions. They have been isolated from marine mollusks, sponges and cyanobacteria, terrestrial and marine microorganisms, particularly endophytic fungi. In an attempt to bring all these strands together, this review will consider the structure, chemistry, biosynthesis, bioactivity, distribution and ecology of this diverse group of metabolites.

Advances in chemical synthesis of carbasugars and analogues

Abstract: Carbasugars, carbocyclic structures where a carbon atom – usually a methylene – replaces oxygen in the heterocyclic motif of the carbohydrates, represent an important class of natural and synthetic compounds that exhibit far-reaching biological effects. In this article the carbasugars have been divided into three main categories, those embodying a cyclopentane motif (furanoid carbasugars), those incorporating a cyclohexane motif (pyranoid carbasugars), and those bearing rather rare cyclopropane, cyclobutane, cycloheptane, and cyclooctane cores (contracted and expanded carbasugars). In the three major sections of this article, the most representative syntheses of the carbasugars and their closest analogues are analyzed, and the key carbocycle forming manoeuvres are focused on in particular detail. Reference to the observed biological activity is also included, where sufficient data is available. Only recent literature from the 90s onwards was considered, although the most pioneer works on this matter have also been remembered. Lack of space did not permit us to cover this field completely; however, in order to offer the reader a wider coverage of this subject matter, two tables listing important review articles and papers dealing with carbasugars, not discussed in the text, have been included in the final section of this account.

Chemistry and Biological Activities of Isoprenylated Flavonoids from Medicinal Plants (Moraceous Plants and Glycyrrhiza Species)

Abstract: Among a large number of phenolic compounds isolated from natural source, various isoprenoid-substituted phenolic compounds have often been found in plants. Moraceous plants and licorice ( Glycyrrhiza species) are rich sources of the isoprenoid-substituted phenolic compounds, including flavonoids. Some of the Morus flavonoids, such as kuwanons G and H, have been regarded as optically active Diels-Alder type adducts. Furthermore, some of the isoprenylated-flavonoids from the moraceous plants and licorice showed the interesting biological activities. This article reviews the biological activities of the isoprenylated-flavonoids from the root barks and/or barks of moraceous plants and from Glycyrrhiza species by our group. The chemical studies concerning the biological activities of these compounds are also described briefly.

Ecdysteroid Structure-Activity Relationships

Abstract: The purposes of this review are i) to provide a compilation of the biological activity data for insect steroid hormones (ecdysteroids) and ii) to summarise the findings concerning their structure-activity relationships (SAR), the contexts within which they are performed and their applications. All ecdysteroid SAR studies have been considerably helped by the availability of ecdysteroid analogues (phytoecdysteroids) in certain plant species, where they occur in much higher concentrations and with greater structural variety than in arthropods. Initial SAR studies, using a variety of bioassay systems were of necessity fragmentary and empirical. However, they led to some very important conclusions about the structural features of ecdysteroids associated with biological activity, which largely still stand today. However, a number of technical advances have revolutionised what is possible in ecdysteroid QSAR since the beginning of the 1990s. Firstly, with the cloning and characterisation of ecdysteroid receptor genes from a number of arthropod species, our understanding of the mode of action of ecdysteroids and their role in signal transduction has greatly increased. Secondly, even minor phytoecdysteroids can be isolated, unambiguously identified and thoroughly purified in amounts suitable for quantiative bioassay. Thirdly, new bioassays have been developed which permit the rapid comparison of the relative potencies of large numbers of analogues. Lastly, the development of powerful computer-based software permits complex QSAR analysis, molecular modelling, activity prediction and analogue design. Recent developments include homology models for the ligand-binding domains of several insect ecdysteroid receptor proteins, Comparative Molecular Field Analysis and 4D-QSAR models for ecdysteroid binding to intracellular receptors. These approaches are generating experimentally testable predictions which are informing synthetic strategies for ecdysteroid analogues. The applications of ecdysteroid QSAR to agriculture and medicine are discussed, especially the design of novel pest control agents and the application of ecdysteroid receptors in gene switch systems for the control of transfected genes in mammalian or plant cells.

Acaricides of natural origin, personal experiences and review of literature (1990-2001)

Abstract: Acari are responsible for millions of dollars worth of damages each year as a result of infestations in animals, plants and man. They affect our health directly and prosperity as animal and plant parasites, vectors of disease, and producers of allergens. The indiscriminate use of pesticides has destroyed many of their natural enemies of hitherto harmless species and quickly induced resistance in many parasites. At present, the control of acarid parasitic diseases in agriculture, human and veterinary medicine is mainly based on the use of drugs; for this reason the lack of effective drugs often prevents the control of some parasitic diseases, making them more serious and important. The use of commercial drugs involves many problems; besides the drug-resistance shown by the most important parasites, the environmental damage and the toxicity of many synthetic drugs, represent the main problems that strongly limit their use. In addition, drug residues in plant and animal food products are important reasons for further economic losses for farmers and must be regarded as potentially hazardous to man and environment. Plant-derived compounds are generally more easily degradable and could show a smaller negative environmental impact with respect to synthetic drugs. For these reasons, the evaluation of the antiacarid activity of plant extracts is increasingly being investigated in order to obtain new leads, as demonstrated by recent studies that have evaluated and confirmed the effectiveness of many plant compounds on bacteria, fungi, protozoa, helmints and arthropods. This review will be limited to the class Arachnida, sub-class Acaridi, particularly to their control in agriculture, veterinary and human medicine with natural methods.

The chemistry and biology of lapachol and related natural products α and β-lapachones

Abstract: This review describes a group of compounds related to the prenyl naphthoquinone lapachol. They exhibit interesting biological activities. Various aspects of the identification, biosynthesis, chemistry and biological properties are discussed.

Podolactones: A Group of Biologically Active Norditerpenoids

Abstract: More than seventy podolactones have been isolated mainly from Podocarpus species. Some of these structures have also been found in filamentous fungi. The different biosynthetic origin of these molecules considering their vegetal or fungic source is discussed in this review. These molecules present a wide range of biological activities: anti-tumor activity, anti-inflammatory activity, fungicide activity, insecticidal activity and plant growth regulatory activity. These biological properties are analyzed in detail, and in the light of their results, structure/activity relationships are discussed. Finally, chemical reactivity, including interconversion reactions, and synthetic approaches to these compounds are summarized.

Chemical and Biological Studies on Licania Genus

Abstract: : This paper reports the phytochemical and biological studies carried out on several species of the Licania genus (Chrysobalanaceae). This genus includes many species mainly distributed in neotropical South American countries such as Venezuela, Brasil, and Mexico, most of them not yet investigated from the chemical and biological point of view. The name Licania derives from the anagram of the indigenous Venezuelan name “Calignia”. Phytochemical studies of these species led to the isolation and structural characterization, by NMR and MS analysis, of many secondary metabolites, mainly flavonoids, and expecially flavonol glycosides, clerodane diterpenes, and triterpenes having the lupane, ursane, and oleanane skeletons. Particularly flavonoids and their glycosides have a chemotaxonomic interest in the genus and in general in the Chrysobalanaceae family. Furthermore, several biological studies were performed on some crude extracts of these plants. They were found to be cytotoxic to cultured human hepatoma (HepG2), colon carcinoma (Caco-2), melanoma B16, and CA-9KB cells. In addition a molluscicidal activity against Biomphalaria glabrata was also demonstrated. Pure triterpenes showed antibacterial activity on Gram positive and yeast and a moderate cytotoxic action against KB assay, while diterpenes showed antifungal properties. Flavonoids were also tested for their antioxidative action as radical scavengers.

Synthetic Studies on Biologically Active Alkaloids Starting From Lactam-Type Chiral Building Blocks

Abstract: This review describes synthetic studies on biologically active alkaloids starting from three lactams. A stereodivergent process for the synthesis of 3-piperidinol alkaloids and the total synthesis of cytotoxic marine alkaloids, clavepictines A, B, pictamine, and lepadin B, were achieved starting from our original lactam-type chiral building block 1 . The synthesis of the proposed structure for dart-poison frog alkaloid 223A and a stereodivergent process for the synthesis of decahydroquinoline-type dart-poison frog alkaloids were achieved from lactam 31 . Finally, synthesis of the revised structure for the above alkaloid 223A and dart-poison frog alkaloid 207I was also achieved starting from lactam 68 .

Chemistry and Biological Activities of Ginkgo Biloba

Abstract: Ginkgo biloba L. is the solo member of the Ginkgoaceae family, and its leaf extract (EGb) has been clinically used for the treatment of cerebral insufficiency. Several experimental studies have demonstrated that EGb has neuroprotective properties against various age-related physiological changes and cerebral injuries induced by ischemia, edema and apoptosis. The major bioactive principles of EGb are recognized to be flavonoids and terpenoids, ginkgolides and bilobalide. Pharmacological actions of EGb and its constituents indude platelet-activating factor antagonism, anti-oxidant and free radical scavenging properties, as well as modulation of neurotransmission, cerebral glucose and lipid metabolism and cerebral membrane fluidity. These effects are involved in the mechanism related to the protective effect of the extract in the central nervous system.

The Chemistry and Pharmacology of the Genus Dorstenia (Moraceae)

Abstract: The genus Dorstenia contains many plants that are used as anti-infection, anti-snakebite and anti-rheumatic remedies in the medicinal plant therapy of several countries in Africa, Central and South America. The genus is now recognized as a rich source of prenyl and geranyl-substituted coumarins, chalcones, flavanones, flavones and flavonols. Three naturally occurring styrenes were reported from D . barnimiana . The geranyl substituted furocoumarin, O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl)butyl]bergaptol, has been found in many species. D . poinsettifolia furnished the unusual substituted 4-phenyldihydrofurocoumarin. Prenylated and geranylated flavonoids have so far been reported only from African Dorstenia species. 5, 3’-Digeranyl-3,4,2’,4’-tetrahydroxychalcone isolated from D . proropens , is the only example of a bis -geranylated chalcone in the literature. A part from 7,8-(2,2-dimethylpyrano-4’-methoxyflavanone (dorspoinsettifolin) from D . poinsettifolia and 3’,4’-(2,2-dimethylpyrano-6-prenyl-7-hydroxyflavanone (dinklagin A) from D . dinklagei , all flavanone derivatives named dorsmanins A - J described here are from D . mannii . These dorsmanins appear to be derived from 6,8-diprenyl-5,7,3’,4’-tetrahydroxyflavanone and a possible biosynthetic scheme for them is presented. D . Zenkeri yield a bichalcone derivative which is believed to arise from dorstenone another prenylated bichalcone isolated from D . barteri . The latter is probably formed via an enzymatic Diels-Alder reaction of 3’-prenyl-4,2’,4’-trihydroxychalcone (isobavachalcone) and its dehydroderivative. D . psilurus provided all the triprenylated flavonoids found so far in Dorstenia and, of these, dorsilurin E is unique having ring B of the flavonoid structure modified to a dienone. The pharmacological data on this genus are scanty. Extracts of D . multiradiata show antileishmanial activity. Extracts and /or compounds from other species show anti-inflammatory, analgesic, anti-oxidant and citotoxic activities.

Bioactive compounds from the genus broussonetia

Abstract: The genus Broussonetia of the Moraceae (mulberry family) is of both ethnomedical and industrial interest. Of the approximately 30 species in this genus, only three have been subjected to previous phytochemical investigation, namely, B. kazinoki, B. papyrifera, and B. zeylanica. From over 100 compounds isolated from these species, the major secondary metabolites reported thus far are alkaloids of the pyrrolidine type and several types of flavonoids. Some of these compounds have exhibited various biological activities, such antioxidative, aromatase inhibitory, cytotoxic, glycosidase inhibitory, and platelet aggregation inhibitory effects. The biologically active constituents of the species in the genus Broussonetia are discussed in detail.

Synthesis and Modification of Marcfortine and Paraherquamide Class of Anthelmintics

Abstract: Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds – preferably with a different mode of action – is an important endeavor. Marcfortine A (1), a metabolite of Penicillium roqueforti, is structurally related to paraherquamide A (2), originally isolated from Penicillium paraherquei. Chemically the two compounds differ only in one ring; in marcfortine A, ring G is six-membered and carries no substituents, while in paraherquamide A, ring G is five-membered with methyl and hydroxyl substituents at C14. Paraherquamide A (2) is superior to marcfortine A as a nematocide. 2-Desoxoparaherquamide A (PNU-141962, 53) has excellent nematocidal activity, a superior safely profile, and is the first semi-synthetic member of this totally new class of nematocides that is a legitimate candidate for development. In this review, total synthesis of paraherquamides was also described.

Prevention of Cancer Chemotherapy Drug-Induced Adverse Reaction, Antitumor and Antimetastatic Activities by Natural Products

Abstract: Although it has recently been 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 antitumor and antimtastatic actions, I have been using biochemical and pharmacological approaches to study the natural products isolated from various medicinal plants and foodstuffs. In the review, we will introduce the biological and pharmacological actions of various components isolated from some medicinal plants and foodstuffs on tumor growth and metastasis in tumor-bearing mice. Chitosan and fish oils prevented the adverse reactions such as gastrointestinal toxicity and myelotoxicity caused by cancer chemotherapy drugs without interfering the antitumor activity of chemotherapy drugs. Stilbenes derivatives isolated from Cassia or Polygonum species inhibited the tumor growth and metastasis to the lung in highly metastaic tumor-bearing mice. Furthermore, I found that stilbenes inhibited the angiogenesis in in vivo and in vitro models.

Total Synthesis Of Biologically Intriguing Drimane-Type Sesquiterpenoids Via Intramolecular Diels–Alder Approaches

Abstract: The total syntheses of three drimane-type sesquiterpenoids, (–)-mniopetal E, (–)-mniopetal F, and (–)-kuehneromycin A, are described. These natural products inhibit the enzymatic activity of RNA-directed DNA-polymerases (reverse transcriptases) of the human immunodeficiency virus (HIV)-1. Our enantiospecific total syntheses of these target molecules in naturally occurring forms commenced with a known 2,3-anhydro- d -arabinitol derivative, which was prepared using the Sharpless asymmetric epoxidation strategy. A combination of highly stereocontrolled inter- and intramolecular Horner–Emmons carbon elongations led to the two butenolides tethering 1,2,4,9- and 1,4,9-functionalized nona-5,7-diene moieties at the β-carbon. The key step in mniopetal E synthesis is a stereoselective thermal intramolecular Diels–Alder reaction of the former butenolide compound, providing a highly oxygenated tricyclic skeleton with the desired endo and π-facial selections. The intramolecular Diels–Alder reaction of the latter butenolide compound for the syntheses of other two drimanes also proceeded with the desired stereoselectivity, which is controlled by a balance of the steric effect and the stereoelectronic effect of a trialkylsilyloxy substituent existing adjacent to the dienophile in accordance with Cieplak’s theory. The transformation of the γ-lactone moiety in the cycloadducts to the γ-hydroxy-γ-lactone part was efficiently achieved via a tetracyclic intermediate. Our total syntheses of (–)-mniopetal E, (–)-mniopetal F, and (–)-kuehneromycin A established the unsettled absolute stereochemistries of the antibiotics. In addition, the reported total syntheses by Jauch are briefly reviewed.

The biosynthesis and properties of anti-carbohydrate antibodies

Abstract: Antibodies are an important group of bioactive natural products and are of the globulin class of proteins. Anti-carbohydrate antibodies are produced by immunization of animals with carbohydrate containing antigens. The antigens may be a polysaccharide, glycoprotein, glycolipid or a synthetic conjugate of carbohydrate and protein. The antibody that is produced is polyclonal and has specificity for the carbohydrate residue of the antigen. Many types of anti-carbohydrate antibodies have been isolated in pure form by affinity chromatography. These are specific for mono- or disaccharide units of antigens (e.g. glucose, galactose, mannose, rhamnose, fucose, glucuronic acid, N-acetyl glucosamine, lactose, isomaltose, lactosamine, neuraminic-galactose, glucuronic-galactose, mannose-glucuronic, rhamnose-glucuronic, arabinose-glucuronic, me glucuronic-galactose). The chemical and biological properties of these antibodies have been determined. To illustrate, molecular weight, light and heavy chain type, immunoglobulin class, inhibition, ultracentrifugation, electrophoresis, isoelectrofocusing and specificity are recorded. Many of these anti-carbohydrate antibodies have been useful in applications. Some have been used in medicine for the identification of pathogenic microorganisms, some in studies to determine the structure of carbohydrate polymers, some for the analysis of additives to processed food and beverages and some in pharmaceutical uses to prepare vaccines for treatment of diseases.

Search for Bioactive Natural Products from Unexploited Microbial Resources

Abstract: The Myxomycetes (true slime molds) are an unusual group of primitive organisms that may be assigned to one of the lowest classes of eukaryotes. As their fruit bodies are very small and it is very difficult to collect much quantity of slime molds, few studies have been made on the chemistry of myxomycetes. Cultivation of the plasmodium of myxomycetes in a practical scale for natural products chemistry studies is known only for very limited species such as Physarum polycephalum . We recently studied the laboratory-cultivation of myxomycetes and several species have been successfully cultured in agar plates. Chemical constituents of cultured plasmodia of several species of myxomycetes of the genera Didymium and Physarum were examined to obtain several sterols, new lipid, or pyrroloiminoquinone derivatives. Previous studies on the chemistry of the secondary metabolites of myxomycetes by other groups are also described here.

Recent Progress in Retinoid Chemistry

Abstract: Natural retinoids, especially retinol, are present in all living organisms. They are known as fundamental mediators for many biological processes, e.g. vision, cellular growth, differentiation of epithelial tissue, reproduction, etc. Although retinol is an omnipotent compound, natural retinoids like all E , 9 Z and dehydroretinoic acids are clearly more potent outside the retina and trigger gene expression via binding to nuclear retinoid receptors. Retinaldehyde occupies an intermediate position in this respect, with the ability to convert to both retinol and retinoic acid (RA). Retinol has an exceptional position among the retinoids, both in terms of production and its field of applications. In 1995, the sales of retinol reached US $ 500 million. Considering the interplay between the stereochemistry of retinoids and their biological activities, any synthetic approach to these compounds must meet the requirement of stereochemical control, in order to obtain the desired isomer in a highly stereoselective manner. Despite the recent achievements in the preparation of conjugated E/Z-dienes and trienes using a variety of synthetic procedures, there is still a need for versatile and efficient approaches to higher unsaturated E/Z-polyolefins with the appropriated configuration. This review covers the major synthetic literature on natural retinoids from 1990 to the present.

Promising pharmacological actions of croon in crocus sativus on the central nervous system

Abstract: Information on clinically available activities in both peripheral and neuronal systems of crocin in saffron has been accumulated. The LTP-blocking effect of ethanol was significantly improved by oral-, intravenous-, and intracerebroventricular-administration of crocin, respectively. We investigated the effects of ethanol and crocin on synaptic potentials mediated by N-methyl-D-aspartate (NMDA) receptors in the dentate gyrus of rat hippocampal slices. Crocin alone did not affect synaptic potentials mediated by non-NMDA or NMDA receptors. Crocin did not affect the inhibition of non-NMDA response by 100 mM ethanol, but significantly blocked the inhibition of NMDA response by 10-50 mM ethanol. We performed whole-cell patch recording with primary cultured rat hippocampal neurons, and confirmed that crocin blocked ethanol inhibition of inward currents evoked by the application of NMDA. We also demonstrated that crocin suppresses the effect of tumor necrosis factor (TNF)-α on neuronally differentiated PC-12 cells. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-α-induced release of cytochrome c from the mitochondoria. Crocin also blocked the cyotochrome c-induced activation of caspase-3. We found that crocin inhibited the effect of daunorubicin as well. The present paper focuses on the pharmacological actions of crocin on the central nervous system and reviews briefly the findings of such studies on the prevention of neuronal programmed cell death (apoptosis).

Halogen-Containing Antibiotics From Streptomycetes

Abstract: Thousands of new structures of organic compounds have so far been described in the genus Streptomyces, the best-known producer of antibiotics Streptomycetes are the most thoroughly studied microorganisms producing biologically active compounds; out of them several tens contain a halogen atom in their molecules Mainly is chlorine, however, brominated and fluorinated compounds have also been described The main attention was devoted to strains producing industrially manufactured antibiotics such as chloramphenicol, chlortetracycline, or the group of antibiotics of vancomycin type However, other halogenated metabolites also exhibit interesting biological effects It will be the aim of this chapter to describe the occurrence, isolation, structure and occasionally also biosynthesis of these metabolites

Synthesis of Bioactive Diterpenes

Abstract: This article reviews the literature published dealing with the synthesis of some bioactive diterpenes. It describes the biological activity and synthesis of only four diterpenes: pisiferic acid, carnosic acid, triptolide and miltirone. This review excludes the discussions of Taxodione, a bioactive diterpene, because it has already been reviewed [85] . The utility of several reagents in the total synthesis of terpenoid compounds has been documented. It can be observed that several routes have been developed for the synthesis of a single diterpene.

Antitumoral Activity of Lipids a Studies in Animal Models and Cancer Patients

Abstract: LPS consist of an O-specific chain, a core and a lipid A. It brgan to be used as a tumor therapy since the XIX century, but it became clear in the 1980s that the biological activity of LPS is due to their lipid A component. LPS and lipid A interact with membrane receptors on target cells which initiate signal transduction. The end result of the intracellular signaling is mainly the activation of NFϰB and AP-1, which then induce the expression of diverse genes such as cytokines, adhesion molecules, etc. Thus the antitumoral effect of LPS and lipid A is indirect and relies on the induction of an immune response, both innate and acquired. These components affect tumor development mainly inhibiting tumor blood flow and inducing necrosis as well as apoptosis of the tumor cells. Cancer treatments with LPS and lipid A have been tested in animal models as well as at the clinical level, either alone or as adjuvants in therapeutic vaccines. In animals, these treatments have achieved certain efficacy, which depends on the type of molecule and the protocol used. In general, an increased survival has been obtained, accompanied in some cases of tumor regression and cure. In clinical trials, the induction of an immune response has been evidenced, but the results are so far too preliminary to permit a definite conclusion. Nevertheless, these components represent a hope for cancer patients and now it is necessary to extend the studies to clinical phase ΙII trials.