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Ensuring interoperability between WebGIS applications is essential for maximizing access to data, data sharing, and data manipulation. Interoperability is maximized through the adoption of best practices, use of open standards, and utilization of spatial data infrastructure (SDI). While many of the interoperability challenges like infrastructure, data exchange, and file formats are common between applications, some regions like the Arctic present specific challenges including the need for presenting data in one or more polar projections. This paper describes the Arctic Research Mapping Application (ARMAP) suite of online interactive maps, web services, and virtual globes (the ARMAP suite; http://armap.org/) and several of the interoperability challenges and solutions encountered in development to date. ARMAP is a unique science and logistic tool supporting United States and international Arctic science by providing users with the ability to access, query, and browse information and data. Access to data services include a text-based search utility, an Internet Map Server client (ArcIMS), a lightweight Flex client, ArcGIS Explorer and Google Earth virtual globes, and Open Geospatial Consortium (OGC) compliant web services, such as Web Map Service (WMS) and Web Feature Service (WFS). Through the ARMAP suite, users can view a variety of Arctic map layers and explore pertinent information about United States Arctic research efforts. The Arctic Research Logistics Support Service (ARLSS) database is the informational underpinning of ARMAP. Avoiding duplication of effort has been a key priority in the development of the ARMAP applications. The ARMAP suite incorporates best practices that facilitate interoperability such as Federal Geographic Data Committee (FGDC) metadata standards, web services for embedding external data and serving framework layers, and open standards such as Open Geospatial Consortium (OGC) compliant web services. Many of the features and capabilities of ARMAP are expected to greatly enhance the development of an Arctic SDI.

Ethnopharmacological relevance Plants of the family Amaryllidaceae are used widely in traditional medicine in South Africa. Several of these, including representatives of the genus Cyrtanthus find use in the treatment of mental illness and age-related dementia. Aim of the study Based on the distribution of central nervous system-activating alkaloidal constituents within the genus Cyrtanthus , Cyrtanthus contractus was here explored for such compounds which could interact with acetylcholinesterase (AChE), of significance in the progression of neurodegeneration associated with Alzheimer's disease. Materials and methods The known phenanthridone alkaloid narciprimine was isolated via column chromatography of the ethanolic extract of bulbs of Cyrtanthus contractus . The structure of the compound was determined by high field 2D NMR and mass spectroscopic techniques. The classical method of Ellman et al. was used in the determination of AChE inhibitory activity. Results The isolation of narciprimine from Cyrtanthus contractus is a landmark find since it has previously only been identified in Zephyranthes , Narcissus and Lycoris , genera endemic to the Americas, Europe and Asia, respectively. Narciprimine exhibited micromolar inhibitory activity (IC 50 78.9) against the enzyme acetylcholinesterase. Conclusion This work represents the first isolation of narciprimine from an African Amaryllidaceae species, which may be of chemotaxonomic significance. The AChE inhibitory activity of narciprimine, taken together with activities of other structurally similar inhibitors within the series affords further insight to the structural details of the lycorine alkaloid acetylcholinesterase inhibitory pharmacophore.

Most water management studies concentrate on the inter-temporal allocation problem or, more recently, spatial dynamics – but not both. While early spatial–temporal studies focused on the allocation of water quantity, this paper presents an approach to water quality analysis that incorporates both spatial and temporal dynamics in a watershed framework. The acid mine drainage (AMD) problem in the Cheat River watershed of West Virginia, USA, serves as a case study and provides an opportunity to test the modeling approach developed. The empirical models are written in General Algebraic Modeling System (GAMS) and solved using the CPLEX mixed integer programming package. The results suggest that available investments should be concentrated in heavily impaired stream segments. The model can be used to assess the economic implications of alternative watershed Total Maximum Daily Load (TMDL) implementation or other management strategies.

Apoptosis-inducing anticancer drugs have garnered widespread interest in recent years. Targets which concomitantly also exhibit minimal adverse effects in normal, healthy cells have been particularly well-received. The phenanthridone alkaloids such as pancratistatin and narciclasine exemplify such a class of chemotherapeutics, with potent and selective cytotoxic effects in a wide variety of cancer cells which are manifested via the apoptotic mode of cell death. Caspases are central to the apoptotic process through their key function as effector molecules in apoptosis-related signaling pathways. Any attempt to mediate in such pathways, for example to probe the efficacy or mechanism of action of a drug, would inexorably serve to have a modulatory effect on these proteolytic enzymes. Apoptosis studies of phenanthridone alkaloids of the Amaryllidaceae have only gathered momentum over the past decade, following which caspases have understandably emerged as reliable biochemical markers of the process in an assortment of cancers. This review covers such studies of these alkaloids based on their structural-type, pointing out the various caspases which have been activated in different cancer cells and how structure modification can to a certain extent have a bearing on such activity. Also considered are clues to the apoptosis signaling pathways mediated following phenanthridone-induced activation of caspases.

The synthesis of differentially functionalized analogs of the Amaryllidaceae alkaloid lycorine, accessed via a concise chemoselective silylation strategy, is described uncovering two of the most potent inhibitors of acetylcholinesterase (AChE) identified to date in this series. Important elements of this novel pharmacophore were elucidated through structure-activity relationship (SAR) studies.

seco-Derivatives of the anticancer agent pancratistatin bearing the 2S,3S,4S,5S configuration were accessed via a novel, highly diastereoselective anti-aldol reaction. Structure–activity relationships reveal important insights into the seco-pancratistatin pharmacophore as a potent and selective inhibitor of human cytochrome P450 3A4 (CYP3A4), and highlight features of concern in advancing a potent, selective anticancer agent in the pancratistatin series.

The growth in demand for cosmetic, graft and organ transplant surgical procedures, the increased use of antineoplastic and immunosuppressive agents, as well as multidrug resistance are some of the factors responsible for the marked rise in fungal infection rates in recent years. Consequently, there have been renewed calls from both the public and private sectors for new and improved drug targets to replace existing antifungal therapies, many of which have been in clinical circulation for several decades. Plants select themselves in such endeavors owing to their superior numbers and vast chemical diversities. With this as a backdrop, this survey examines the antifungal activities of Amaryllidaceae plant extracts against various fungal pathogens. Good growth inhibitory activities (MICs

The relationship between primary and scrap prices has been hypothesized for the most part as unidirectional, characterized by spillovers from primary to scrap prices. The purpose of this study is to evaluate empirically the dynamic interactions between primary and scrap metal prices through multivariate time series methods. In addition, the study expands the investigation at the level of volatility transmission, which has not been previously examined. The metal prices utilized are for copper, lead, and zinc for the period 1984–2001. The paper demonstrates differing long run and short run links. Scrap prices do not improve the long run interpretation of primary prices, but information flows from the scrap to the primary markets exist in the short run. Additionally, the copper and lead markets exhibit bidirectional information flows in terms of volatility transmission. The analysis provides valuable insight into the interactions of the primary and scrap metal sectors which can be used to improve forecasting and planning.

The monodentate ligand 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phospha-adamantane (PA-Ph) is shown to be highly effective in palladium-catalyzed carbonylative cross-coupling. Aryl and vinyl halides were efficiently converted to carboxylic acids, amides and to primary, secondary, and tertiary esters, respectively. Application of the Pd(OAc)2/PA-Ph (1:1) catalyst system proved critical in the methoxycarbonylation of a functionalized nitroresorcinol halide, allowing convenient access to novel platensimycin sulfonamide analogs.

A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and the natural compound narciclasine exhibited low micromolar activities. Important pharmacological features uncovered include the lack of CYP3A4 inhibitory activity seen for galanthamine and the selective activity that is seen with narciclasine over pancratistatin.

The use of the ligand bis(di-tert-butylphosphino)-o-xylene (dtbpx) in palladium-catalysed carbonylative and Suzuki–Miyaura cross-coupling reactions is described. Aryl and vinyl halides readily entered into the carbonylative catalytic cycle affording carboxylic acids, amides as well as primary, secondary and tertiary esters, respectively, in good yields. Aryl iodides, bromides and chlorides gave high yields of biphenyl products upon reaction with both activated and unactivated boronic acids.

Graphical abstract The direct chemoselective differential functionalization of the ring-C hydroxyl groups present in the Amaryllidaceae alkaloid lycorine is described allowing for selective manipulation of the 1,2-hydroxyl groups. A mini-library comprised of synthetic and natural lycorane alkaloids was prepared and their apoptosis-inducing activity investigated in human leukemia (Jurkat) cells. Further insights into the nature of this interesting apoptosis-inducing pharmacophore are described, including the requirement of both free hydroxyl groups in ring-C., The direct chemoselective differential functionalization of the ring-C hydroxyl groups present in the Amaryllidaceae alkaloid lycorine is described allowing for selective manipulation of the 1,2-hydroxyl groups. A mini-library comprised of synthetic and natural lycorane alkaloids was prepared and their apoptosis-inducing activity investigated in human leukemia (Jurkat) cells. Further insights into the nature of this interesting apoptosis-inducing pharmacophore are described, including the requirement of both free hydroxyl groups in ring-C.

The suitability of applying the NRCS curve number (CN) to continuous runoff prediction is examined using a new technique of back-calculating CN values from the output of a complex nonlinear hydrolo...

PurposeThe purpose of the study is to evaluate the impact of China's current coal‐to‐liquids (CTL) activities on its coal and oil markets from 2005 to 2025.Design/methodology/approachA partial equilibrium multi‐equation model of China's oil and coal markets is developed based on data obtained from the existing literature. The impact of CTL technologies on China's oil and coal markets is evaluated using computer simulations by solving the model under scenarios with and without CTL production.FindingsThe simulation results show that on average, the planned CTL activities will decrease crude oil prices by 5.73 percent and China's oil imports by 6.09 percent and increase China's domestic oil supply by 9.26 percent over the 20 year period. Also, China's demand for oil will increase by 0.35 percent on average, suggesting that CTL production will slightly stimulate China's demand for oil because of the drop in oil prices. China's demand for coal will also increase by 1.02 percent because of the additional demand for coal created by CTL production. Surprisingly, both coal prices and China's coal supply will decline by 0.51 percent while the demand for coal and coal supply of the rest of the world will be reduced by 1.63 percent and 0.28 percent, respectively.Originality/valueThe paper is the first study on the implication of CTL conversion from an economist's point of view. It applies an economic model to quantify the impacts of such technology on overall energy prices and supplies.

The magnesium chloride catalyzed anti-aldol reaction of phenyl acetate derived oxazolidinones proceeds readily with enolizable L-threose derivative 8 to provide anti-aldol adducts in high yields and with very high diastereoselectivities. The reaction is also efficient with aromatic aldehydes and provides slightly lower diastereoselectivities. This extension

Understanding tropical succession requires insight into propagule availability, which constrains possible woody plant recruitment, yet seed rain composition in multiple post-agricultural sites has seldom been examined. We monitored seed rain for 60 wk in five abandoned pastures in southern Costa Rica, collecting a total of 1 140 688 seeds of 165 morphospecies. Most seeds (80.1%) arrived during the wet season. Species richness was highest in the wet season and greater in forest than in pasture. Seed rain density was greatest at the forest/pasture edge and decreased drastically just a few metres into pastures. In and near the forest, animal-dispersed seeds were more abundant than seeds dispersed by other means, while wind-dispersed taxa increased in relative importance at greater distances from the forest. Total seed input to pastures did not reflect size of adjacent forest fragments, although seed rain density varied more than threefold among sites. Among-site variation in density of regenerating woody seedlings was roughly proportional to among-site variation in seed rain. Morphospecies composition differed significantly among sites. Also, seed rain and woody plant colonists were rather dissimilar in composition, suggesting that while propagule availability is necessary for early woody plant establishment, it is a poor predictor of successional trajectory.

The Amaryllidaceae occupies a privileged status amongst medicinal plants in having delivered the Alzheimer's drug galanthamine to the clinical market. Following its resounding success, there have been several positive indicators for the emergence of an anticancer drug from the family due to the potent antiproliferative activities manifested by several of its alkaloid constituents. Of these, the phenanthridones such as pancratistatin hold most promise as potential chemotherapeutics having succumbed to various phases of clinical trials. Other cytotoxic targets of the Amaryllidaceae are to be found within the lycorane and crinane groups, as exemplified by crinine and lycorine. Although the molecular targets of these alkaloids still remain elusive, much effort has gone into understanding their mode of action in cancer cells. Recent findings have shown that the apoptotic pathway may be a key factor in cancer cell death instigated by Amaryllidaceae alkaloids. As such, this review seeks to: (a) examine the apoptotic effects of Amaryllidaceae alkaloids in cancer cells; (b) explore the molecular basis to these effects; and (c) provide a pharmacophoric rationale in support of these activities.

The oil and gas industry has adopted several methods to obtain insight as to how a fluid may affect reservoir material. The Capillary Suction Time (CST) test has become a de facto standard test method, largely due to its simplicity and speed. The most obvious shortcoming of the CST test is that it introduces a medium (paper) that is far different from anything found in an actual reservoir; in fact, one may argue that the CST test is essentially a measure of the interaction of the test fluid with the paper. The lack of theoretical foundation of the CST test precludes reproduceable results or proper estimation of errors in measurement. We present a new test method that observes only intrinsic properties of the formation in contact with a test fluid, bolstered by a strong theoretical basis, in stark contrast to the CST test. Our method preserves the desirable attributes of the CST test, but replaces imbibition into paper with imbibition into reservoir material. The method uses a comminuted sample, and the results from the imbibition step are used to determine formation wettability in the form of the advancing contact angle. The results from a subsequent drainage test are used to determine the receding contact angle, and the capillary pressure versus saturation curve. Prior to performing the drainage test, test fluid is placed on top of the saturated pack and the permeability of the pack to the test fluid is determined. The permeability of the pack to liquid is then compared to the pretest permeability of the pack determined using nitrogen. Use of this pack as a testing environment allows the technique to be applied to formation samples of virtually any permeability and porosity. We have found that there is no correlation between CST test data and the permeability data obtained using the new method presented here. We present several cases in which a positive result from a CST test is inconsistent with the results obtained from the new test method. We maintain that the discrepancies cast serious doubts on the general applicability of the CST test as a tool for studying rock/fluid interactions. In summary, there is a great need to standardize testing that investigates rock/fluid interactions. The widely used CST method introduces a foreign material and it does not offer sufficient resolution, reproducibility, or estimation of error. Even if the CST method were adequate, the lack of standardization in testing and analysis methodologies makes comparisons of published results difficult. Our method provides superior results. The strong theoretical foundation of the new method allows rigorous analysis making comparisons between treating fluid options far more trustworthy.

This paper continues previous work in which we developed the Galois theory of strongly normal extensions using differential schemes. In the present paper we derive two main results. First, we show that an extension is strongly normal if and only if a certain differential scheme splits, i.e. is obtained by base extension of a scheme over constants. This gives a geometric characterization to the notion of strongly normal. Second, we show that Picard-Vessiot extensions are characterized by their Galois group being affine. Our proofs are elementary and do not use "group chunks" or cohomology. We end by recalling some important results about strongly normal extensions with the hope of spurring future research.

The [Rh(acac)(CO)(L)] (acac = acetylacetonato; L1 = 1,3-bis-(2,6-diisopropylphenyl)imidazolinylidene and L2 = 1,3-bis-(2,4,6-trimethylphenyl)imidazolinylidene) complexes were prepared by the action of the parent carbene on [Rh(acac)(CO)2] in THF. The crystal structure characterisation of [Rh(acac)(CO)(L1)] revealed a slightly distorted square planar geometry with the carbene ligand orientated almost perpendicular to the equatorial plane; an elongated trans Rh–O bond of 2.0806(18) A reflecting the considerable trans-influence of the carbene ligand. By measuring the CO stretching frequencies in a range of [Rh(acac)(CO)(L)] complexes (L = CO, L1, L2, PPh3, PnBu3, P(O–2,4-tBu2–Ph)3) the following electron donating ability series was established: L1 ∼ L2 ∼ PnBu3 > PPh3 > P(O–2,4-tBu2–Ph)3 > CO; indicating the carbenes investigated in this study to have a similar electronic cis-influence as trialkyl phosphines. Both complexes do not display hydroformylation activity towards 1-hexene in the absence of added phosphine or phosphite ligands under the conditions investigated (P = 60; T = 85 °C). In the presence of a phosphine or phosphite ligand the resulting hydroformylation catalysis was identical to that observed for [Rh(acac)(CO)2] and the corresponding ligand and subsequent high-pressure 31P NMR studies confirmed substitution of the carbene ligand under these conditions.

As the cost of production is a key determinant of long-term viability, developing methods that reduce the cost of direct coal liquefaction has posed a challenge to scientists and industrial organizations worldwide. This paper summarizes recent developments in technology and processes and explores the overall economic competitiveness of direct coal liquefaction using the China Shenhua Group Corp. (Shenhua) project as a case study. A comparative analysis of the costs and economic competitiveness of the Shenhua approach and a variety of conceptual designs outlined in U.S. studies is presented. The comparison shows that the economic competitiveness of direct coal liquefaction is dependent on production costs that consist primarily of raw material, operation and management, and capital costs. Capital cost is shown to be a primary determinant of the cost of production. The relative competitiveness of the plant and supporting facilities depends heavily on the economic alternatives relevant to a particular plant ...

The novel compounds N-demethylbelladine, 6α-methoxybuphanidrine and filifoline, in addition to five known alkaloids, and phenol have been isolated from fresh bulbs of Nerine filifolia (Amaryllidaceae). The structure and stereochemistry of the compounds were determined by physical and spectroscopic methods, including 1D and 2D NMR and mass spectroscopic techniques. An unusual circular dichroism response from filifoline has required a semi-synthetic derivatisation strategy towards key C-11endo analogues of the β-crinane representative ambelline in which the nature of substituents was observed to have a profound effect on molecular ellipticity. Filifoline was not cytotoxic to myoblast (L6) cells and exhibited no anti-protozoal activity in an in vitro screen against four different parasitic protozoa.

The discovery of karrikins as the chemical constituents responsible for the germination stimulatory effects of smoke has met with widespread interest from the botanical/scientific community. Although such beneficial properties of smoke in agriculture and environmental management have been known for several centuries, it is only in the last decade that this significant discovery has been made. The karrikins comprising KAR1–KAR6 have been shown to be potent promoters of germination in numerous model studies. KAR1, the most abundant of the karrikins, has been revealed as the key germination cue present in smoke with activities as low as 100 ppt. Given the vast economic potential of these molecules as well as their low natural abundance, several strategies have been devised towards the synthesis of karrikins with the goal of elucidating structure–activity relationships. However, the targets of these structures as well as their mode of action are yet to be determined. To this end, we herein detail the first single crystal X-ray structure of KAR3 with the aim that it may provide further insights to the molecular mechanism behind this group of compounds.

The plant family Amaryllidaceae is known for its ornamental and medicinal value, as well as its unique alkaloid constituents, including several molecules of high biological interest, such as galanthamine, pancratistatin and lycorine. These plants are also used in traditional medicinal practice systems across the globe, and the taxonomy of the family is relatively well-understood. The African genus Boophone Herb. comprises two species, B. disticha (L.f.) Herb. and B. haemanthoides F.M. Leight. Much is known about the ethnobotanical, phytochemical and pharmacological properties of the wide-ranging B. disticha. In contrast, B. haemanthoides is a threatened and territorially restricted species, and its ethnobotanical usage by Khoi-San of the Northern Cape has only recently been described. During our investigation, B. haemanthoides was shown to be a novel source of the known β-crinane alkaloids distichamine, buphanidrine, buphanisine, and crinine. Of note is the presence of distichamine in B. haemanthoides, previously identified only in B. disticha, and its significance as a distinctive chemotaxonomic marker for the genus Boophone.

A catalyst system consisting of a chromium source, a 2,6-disubstituted phenol and an aromatic ether solvent, on activation with triethylaluminium, is active and selective for the trimerisation of ethylene to form 1-hexene. The aromatic ether appears to play a role as both solvent and reagent and is pivotal in ensuring both the good activity of the system as well as selectivity to the desired product, 1-hexene.

Differential Galois theory, the theory of strongly normal extensions, has unfortunately languished. This may be due to its reliance on Kolchin’s elegant, but not widely adopted, axiomatization of the theory of algebraic groups. This paper attempts to revive the theory using a differential scheme in place of those axioms. We also avoid using a universal differential field, instead relying on a certain tensor product. We identify automorphisms of a strongly normal extension with maximal differential ideals of this tensor product, thus identifying the Galois group with the closed points of an affine differential scheme. Moreover, the tensor product has a natural coring structure which translates into the Galois group operation: composition of automorphisms. This affine differential scheme splits, i.e. is obtained by base extension from a (not differential, not necessarily affine) group scheme. As a consequence, the Galois group is canonically isomorphic to the closed, or rational, points of a group scheme defined over constants. We obtain the fundamental theorem of differential Galois theory, giving a bijective correspondence between subgroup schemes and intermediate differential fields. On the way to this result we study certain aspects of differential algebraic geometry, e.g. closed immersions, products, local ringed space of constants, and split differential schemes.

Cells cultured from Alzheimer disease leptomeninges or skin were grafted into the cortex of adult thymectomized rats. At 3 days post-implant, plaque-like aggregates were found in the cortex, corpus callosum, septum and caudate nucleus. These structures were immunopositive for human amyloid precursor protein (APP), human amyloid beta peptide (Aβ), cathepsin D, apolipoprotein E and ubiquitin. Aberrant tau + neurites, reactive astrocytes and microglia were associated with many aggregates. Although birefringent amyloid occupied the central area of most aggregates, these structures had disappeared by l month post-implant. Aβ and APP produced by grafted non-neural human cells can penetrate rat brain and form plaque-like structures, which can be effectively cleared by the rat.

The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, Amaryllis belladonna, has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the native people. In this study, A. belladonna samples collected in Brazil were examined for alkaloid content. Alkaloid profiles of A. belladonna bulbs were generated by a combination of chromatographic, spectroscopic and spectrometric methods, including GC–MS and 2D NMR. In vitro screening against four different parasitic protozoa (Trypanosoma cruzi, T. brucei rhodesiense, Leishmania donovani and Plasmodium falciparum) was carried out using the A. belladonna crude methanol extract, as well as three of its alkaloid isolates. Twenty-six different Amaryllidaceae alkaloids were identified in the A. belladonna bulb samples, and three of them were isolated. Evidence for their respective biosynthetic pathways was afforded via their mass-spectral fragmentation data. Improved data for 1-O-acetylcaranine was provided by 2D NMR experiments, together with new 1H-NMR data for buphanamine. The crude extract and 3-O-acetylhamayne exhibited good antiprotozoal activity in vitro, although both with a high cytotoxic index.

The remediation of infectious diseases is an ongoing concern in healthcare structures due to the continued loss of efficacies of existing schedules and, in particular, the poignant threat of multidrug resistance. In the search for new therapies plants have emerged as an attractive option owing to their vast chemical resources. Allied to this feature is the widespread use of plants in traditional approaches towards infectious diseases. As far as the family Amaryllidaceae is concerned, around fifty of its members are identifiable with such distinctive functions in traditional medicine. This review examines the in vitro antibacterial activities of its plant extracts and sheds light on instances where these are corroborative of the traditional usage.

Globalization and multidrug resistance are amongst the factors implicated in the resurgence of infectious diseases in recent years. This has fostered a compelling need in drug discovery to replace (or supplement) existing schedules. The floral biodiversity has been identified as a viable resource platform due to its inimitable chemical characteristics as well as the presence of numerous of its members in traditional medicinal approaches towards these diseases. Whilst the plant family Amaryllidaceae is conventionally associated with cancer and motor-neuron disease therapies, this survey shows that it has a significant presence in the remediation of infections and infection-related ailments. This verifiable indigenous knowledge could amplify efforts towards the identification of the active chemical constituents.

The plant family Amaryllidaceae is renowned for its unique alkaloid constituents which possess a significant array of structural diversity. Several of these alkaloids are known for their interesting biological properties, of which galanthamine and pancratistatin have acquired a privileged status due to their relevance in the pharmaceutical arena. In particular, galanthamine represents the first prescription drug emanating from the Amaryllidaceae after its approval by the FDA in 2001 for the treatment of Alzheimer's disease. Following on this commercial success there have been sustained projections for the emergence of an anticancer agent related to pancratistatin due to the potency, selectivity, low toxicity and high tolerability typifying targets of this series of alkaloids. The lycorine series of alkaloids have also garnered widespread interest as cytotoxic agents and were amongst the earliest of the Amaryllidaceae constituents to exhibit such activity. To date over 100 of such naturally-occurring or synthetically-derived alkaloids have been screened for cytotoxic effects against a number of cancer cell lines. This survey examines the cytotoxic properties of lycorine alkaloids, highlights the outcomes of structure-activity relationship orientated studies and affords plausible insights to the mechanistic rationale behind these effects.

In this study, the South African Amaryllid Boophone haemanthoides was examined for its phytochemical composition and cytotoxicity. In the process eight alkaloid structures, including the new compound distichaminol, were identified in bulb ethanolic extracts. Of the isolates, lycorine and distichamine exhibited strong activities against human acute lymphoblastic leukemia (CEM), breast adenocarcinoma (MCF7) and cervical adenocarcinoma (HeLa) cells with IC50S ranging from 1.8 to 9.2 microM.

An ongoing search for alkaloids in the Amaryllidaceae species using GC MS resulted in the identification of two crinine-type alkaloids, aulicine (1) and 3-O-methyl-epimacowine, (2) from the indigenous Brazilian species Hippeastrum aulicum and Hippeastrum calyptratum, respectively. In addition, two alkaloids, 11-oxohaemanthamine (3) and 7-methoxy-O-methyllycorenine (4) were both isolated from H. aulicum. Furthermore, we provide here complete NMR spectroscopic data for the homolycorine analogues nerinine (5) and albomaculine (6). The absolute stereochemistry of the 5,10b-ethano bridge in the crinine variants was determined by circular dichroism and X-ray crystallographic analysis, thus presenting the first direct evidence for the presence of crinine-type alkaloids in the genus Hippeastrum.

The cytochrome P45O activities of the naturally occurring Amaryllidaceae alkaloid narciclasine (3), isolated from Narcissus pseudonarcissus, and synthetic derivative trans-dihydronarciclasine (5) are reported. While narciclasine was found to possess potent inhibitory activity to human CYP3A4, its dihydro analogue was inactive. This study revealed that the C1-C10b double bond is required for inhibition of this crucial metabolizing enzyme. Compound 5 also demonstrated no inhibition of the related human cytochromes CYP19 and CYP1A1. This study elevates the status of trans-dihydronarciclasine (5) as a highly privileged, readily available molecule, with potent and selective anticancer activity.

The plant family Amaryllidaceae is known for its horticultural and ornamental appeal as well as its medicinal value. In relation to these characteristics, trade in Amaryllid flower varieties (especially daffodils) is a multi-million dollar revenue generator for the floriculture industry. Of greater significance are the medicinal attributes of the family, which has already spawned the Alzheimer's prescription drug galanthamine, a potent and selective inhibitor of the enzyme acetylcholinesterase, of significance in the progression of neurodegeneration associated with motor neuron diseases, with annual global sales of around $150 million. Furthermore, it is anticipated that an anticancer drug target related to the Amaryllidaceae alkaloid pancratistatin, presently under advanced clinical evaluation, will enter commercial circulation within the next decade. Members of the Amaryllidaceae are distributed through both tropical and subtropical regions of the globe, but are of prominence within three distinct geographical locations, including Andean South America, the Mediterranean basin, and southern Africa. The southern African zone is known to harbor at least a third of the worldwide complement of around 1000 species, many of which are widely utilized in the traditional medicinal practices of the indigenous people of the region. Given its therapeutic and economic value, its natural abundance in the southern African region, coupled to its widespread usage in ethnic medicine, the family Amaryllidaceae provides a diverse and accessible platform for phytochemical based drug discovery. A consolidation of its traditional usage as well as its chemical and pharmacological profiles will thus guide efforts aimed at maximizing this potential. In undertaking this survey of the Amaryllidaceae of southern African, we aimed to achieve these goals.

We determined whether the expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP) in murine macrophages is regulated by the novel synthetic bacterial lipopeptide JBT 3002. Multilamellar liposomes (MLV) encapsulating JBT 3002 (MLV-JBT 3002) stimulated the production of 72-kDa and 92-kDa (gelatinase A and B) type IV collagenase and inhibited the production of murine metalloelastase (MME) in a dose-dependent manner in murine peritoneal macrophages. MLV-JBT 3002 also induced production of TIMP-1. MLV-JBT 3002 did not induce collagenase production in tumor cells. Priming murine macrophages with interferon-gamma (IFN-gamma) inhibited JBT 3002-stimulated production of both MMP-9 and MMP-2 and further inhibited production of MME by a mechanism involving nitric oxide (NO). This conclusion is based on data showing that IFN-gamma failed to inhibit production of MMP in the presence of L-methyl arginine or in macrophages from inducible nitric oxide synthase knockout mice. These data suggest that JBT 3002 differentially regulates the production of various MMPs and TIMP in macrophages.