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• Four genera of the South African Amaryllidaceae surveyed for the period 2013–2020. • These include representatives of Crinum, Ammocharis, Amaryllis and Cyrtanthus. • Shown to have a notable presence in South African traditional medicine. • Such indigenous knowledge systems guide pharmacological evaluation of target species. • Significant findings made in the cancer and motorneuron disease arenas. The plant family Amaryllidaceae has attracted widespread attention in view of the interesting biological properties of its alkaloid principles. Many of these discoveries are based on the traditional usage of its members in regions where they are prominent. Over a third of its complement is found in southern Africa, hence the heightened interest in the Amaryllidaceae from this territory. Up to 2012, over 80 species were examined, mainly for their alkaloid constitution. Given the medicinal potential of the family as well as its widespread usage in South African traditional medicine, efforts over the past decade have intensified in understanding its biological properties. This account focuses on the biological activities that have been reported since 2013 for extracts of four genera of the South African Amaryllidaceae, viz Crinum, Ammocharis, Amaryllis and Cyrtanthus. Fourteen related species were assayed during this period, with Crinum (5 species) and Cyrtanthus (6 species) affording the bulk of the targets. Although most studies utilized the bulbous extracts, there were some instances involving the use of root, leaf and flower materials. The extractants used ranged from water to hexane, with a few examples addressing the outcomes of environmentally-benign extraction procedures. Close to twenty different areas were identified wherein the biological properties of the extracts were examined including, cytotoxicity, AChE and BuChE inhibition, cardio and hypertensive effects, antioxidant and anti-inflammatory effects, as well as antibacterial, antifungal and antiparasitic effects. Some studies also probed the mechanistic basis to these activities, notably in regards to their cytotoxic and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

• South Africa affords a rich and diverse source of Amaryllidaceae plant species. • Boophone, Nerine, Brunsvigia, Strumaria and Crossyne well-represented in the region. • This survey covers biological studies of these five genera for 2013–2020. • Around 20 areas identified in which their extracts have been probed for such effects. • Traditional usage of several of the representative species is also highlighted. The presence of plants in human health and well-being has been trenchant since time immemorial. Some of the most crucial medicines in use today are derived from plant-based materials. Traditional plant usage has played a pivotal role in guiding many of the discoveries that were accomplished in the clinical realm. The plant family Amaryllidaceae is recognized for its interesting biological properties, notably in the areas of cancer and motorneuron disease therapeutics. Its members are well-represented in South Africa, with a proliferation hub centered over its Western Cape Province. Boophone, Nerine, Brunsvigia, Strumaria and Crossyne are genera of the Amaryllidaceae that are prominent amongst the local floral biodiversity. Previous reviews on the biological action of these genera were up to date until 2012. The present account is an update of the field covering material published between 2013 and 2020. It examines the plant parts studied, the solvents utilized in the extraction procedures as well as the biological assays against which the extracts have been screened. These were seen to involve antimicrobial, anti-inflammatory, antioxidant, anticancer, anticholinesterase, cardiovascular, hypertensive and anxiolytic effects. Studies were also identified which addressed the herbicidal and insecticidal effects of some of the plants. Some efforts focused on the molecular basis to the biological activities, notably in regards to anti-inflammatory and anticancer action as well as to motorneuron-related effects. Significant effort is made throughout the text to emphasize the traditional medicinal usage and how such indigenous knowledge has guided the biological evaluation of the plants. [ABSTRACT FROM AUTHOR]

• Five genera of the South African Amaryllidaceae surveyed for the period 2013–2020. • These are inclusive of Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia. • Around 90 isoquinoline alkaloids and 25 non-alkaloidal entities described. • Chemosystematics of selected alkaloids considered. • Biological properties of isolated compounds also described. There is considerable interest in the plant family Amaryllidaceae for its biologically-active isoquinoline alkaloid principles. Some of these (such as galanthamine and narciclasine) have demonstrated their applicability in the clinical arena, particularly as cancer and motorneuron disease therapeutics. While synthetic organic chemistry affords ideal opportunities for drug development with such targets, the phytochemical approach is considered a somewhat more amenable option. In this regard, southern Africa has garnered widespread attention due to the abundance of Amaryllidaceae plants in its territory. Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia are genera of the family that are likewise well-represented in southern Africa. Up to 2012, thirty members from these genera were examined for their chemical and biological properties, culminating with the identification of nearly one-hundred alkaloid entities several of which exhibited notable biological activities. The present effort covers studies since 2013 that have been undertaken on the title genera in regards to their chemical and biological characteristics. Close to ninety alkaloids and twenty-five non-alkaloid entities were described during this time-frame from fifteen representative species. Biological studies included cholinesterase inhibiton, cytotoxicity, antidiabetes and antihypertensive effects, herbicidal, insecticidal and plant growth regulatory effects, as well as anti-inflammatory, antioxidant and antiplasmodial effects. The structural variety of the compounds isolated in cases allowed for structure-activity probes to be made in some of the assays. There were also studies carried out to establish the molecular basis to these activities, notably in the area of molecular cancer chemotherapeutics. [ABSTRACT FROM AUTHOR]

• Tazettine alkaloids of the Amaryllidaceae surveyed for cytotoxic activities. • Eleven of such entities examined in nearly 20 different types of cancers. • Cytotoxicity assays carried out against around 50 different cancer cell lines. • Structural elements of tazettine alkaloids are significant in their activities. • Multidimensional molecular basis to cytotoxicity of tazettine alkaloids uncovered. From camptothecin to vinblastine, plant alkaloids continue to capture the imagination of scientists as a valuable source of anticancer drugs. Given that they are also amongst the most common secondary metabolites encountered in plants, the number of alkaloid entities subjected to cytotoxicity evaluations now runs into several thousands. Interest in the plant family Amaryllidaceae has been persistent owing to the potent cytotoxic activities of several of its isoquinoline alkaloid principles. This survey is an indepth account of such properties discernible for tazettine alkaloids belonging to the minor alkaloid groups of the Amaryllidaceae. Eleven of such compounds have up to now been screened against around 50 cancer cell lines which may be classified into nearly 20 different types of cancers. Although the activities in most instances were moderate to mild, notable responses were observed against some leukemia, adenocarcinoma, lymphoma and glioblastoma cell lines. In fact, pretazettine (ED 50 0.3 μg/mL) was amongst the most potent of all Amaryllidaceae alkaloids screened against the human Molt4 T-lymphoma cell line. To most accounts, the parent compounds (such as tazettine and pretazettine) with their distinct ring systems and substitution patterns exhibit the best activities, offering little space for structural adjustments via semi-synthetic operations. Several avenues have been probed in attempts to elucidate the mechanisms by which tazettine alkaloids manifest their cytotoxic effects including, inhibition of protein synthesis, apoptosis and efflux pump interactions, the first of which to date offers the most profound insights. [ABSTRACT FROM AUTHOR]

• A review of the cytotoxic homolycorine alkaloids of the Amaryllidaceae is presented. • Forty-two of such compounds have to date been screened against 62 cancer cell lines. • Best activity observed for lycorenine against HepG2 hepatoma cells (ED 50 1.2 μg/mL). • Modification of the homolycorine nucleus affords useful insight to cytotoxicities. • Topoisomerase inhibition identified as a key reaction in mechanistic pathways. Stimulated by the promising results seen for its phenanthridones in clinical trials, interest in the Amaryllidaceae as a potential source of anticancer drugs has intensified in recent years. As such, over three hundred isoquinoline principles from its various alkaloid groups have to date been screened against a large number of cancer cell lines. Whilst significant effort has been diverted towards studies of lycorine and its congeners, the closely-allied homolycorine alkaloids of this plant family have largely been overlooked. These compounds have often been used as supporting acts to bolster the diversity of structures in cytotoxicity studies of the more recognized phenanthridone, lycorane and crinane alkaloids of the Amaryllidaceae. This notwithstanding, a substantial amount of information has surfaced over the past several years on such effects for the homolycorine alkaloids. This review takes a detailed look at the cytotoxic effects manifested by over forty of these alkaloids against around sixty cell lines, which may be classified into eighteen different types of cancers. In this regard, good activities were detected for some constituents (such as lycorenine and hippeastrine) against various hepatic and prostate cancers. The structural features which support and fortify the efficacy of the homolycorine alkaloid cytotoxic pharmacophore are also considered. These include the ways in which the innate ring systems are appended as well as the size, geometry and electronics of the attendant substituents. In addition, the various mechanisms used to rationalize the cytotoxic responses are described notably, interaction with DNA, apoptosis induction, protection from tumor invasion, efflux pump perturbation and topoisomerase inhibition. [ABSTRACT FROM AUTHOR]

Malaria is prevalent in tropical and subtropical regions of the globe. With over 200 million cases reported annually, particularly in sub-Saharan Africa, it is an unnecessary burden to already overworked and ailing healthcare structures. Traditional medicine (TM) remains vibrant in most of these regions wherein plants often serve as the first line of defense against malaria. Given this fact as well as the successes elsewhere of therapies such as Artemisia annua emanating from evidence-based TM, interest in plants as a source of new antimalarial drugs has been rejuvenated. The bulbous plant family Amaryllidaceae is recognized for its structurally-diverse alkaloid constituents which exhibit interesting biological properties. This review focuses on the in vitro activities demonstrated by its crinane alkaloids against various strains of the malaria-causing parasite Plasmodium falciparum. The survey embraces the twelve genera of the Amaryllidaceae whose nineteen representative species have been examined for antiplasmodial crinane alkaloid principles. A total of seventy-two compounds were screened against nine strains of P. falciparum , with the α -crinanes reflecting better overall activities than their corresponding β -crinane subgroup congeners. In terms of potency, an ED 50 of 0.14 μg/mL (for augustine in the D-6 strain) and IC 50 of 0.35 μg/mL (for haemanthidine in the K1 strain) were the lowest activity indices observed. Structure-activity relationship studies afforded useful insight on the antiplasmodial pharmacophore and the features supporting its efficacy. Overall, crinane alkaloids have provided a useful platform for the study of antiplasmodial effects, not only in terms of potency but also in terms of structural diversity. The Amaryllidaceae as a source of antiplasmodial crinane alkaloid constituents. Jerald J. Nair, Johannes van Staden. Unlabelled Image • The Amaryllidaceae provides an abundant source of antiplasmodial constituents. • Nineteen species examined for antiplasmodial alkaloids. • Seventy-two crinane alkaloids screened against various Plasmodium falciparum strains. • Activities detected across both chloroquine sensitive and resistant strains. • Haemanthamine and haemanthidine identified with best overall activities. • Haemanthidine (IC 50 0.35 μg/mL) better than mefloquine (IC 50 3.94 μg/mL) in K1 strain. [ABSTRACT FROM AUTHOR]

Abstract The birth, growth, proliferation and death of cells involve a rigorous and continuous process in place to ensure the survival of living organisms. The cell cycle prevails at the core of this process to facilitate the division of a parent cell as well as the duplication of its genetic matter. Although checkpoints exist to steer the course of a cell from one phase to the other, malfunctions at any point of the four active phases of the cell cycle can have detrimental effects. Cancer is thought to be a consequence of such a malfunction in the cell cycle which endows a cell with enhanced replicative potential, immunity to anti-growth signals and the ability to evade apoptosis. This characteristic has been exploited in cancer chemotherapy since a significant number of anticancer drugs manifest their action via cell cycle modulatory effects. The plant family Amaryllidaceae is distinguished for its alkaloid principles which exhibit potent (at the sub-nanomolar level in some cases) and cell line specific antiproliferative activities, with apoptosis induction a key feature of these properties. As a consequence there has been sustained interest in these chemical entities as a source of new anticancer drugs. This has been matched by the large body of work that has emerged over the past two decades addressing their cytotoxic potential, establishing a structure-activity relationship basis as well as probing their mode of action. This review focuses on studies which highlight how Amaryllidaceae alkaloids modulate the cell cycle of cancer cells. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

There is a pressing need in antibiotic drug discovery for new drugs to counterbalance the effects of multidrug resistance. Plants represent a viable platform for such endeavors owing to their traditional relevance in infectious disease therapies as well as their vast chemical resources. As many as fifty different species of the Amaryllidaceae are discernible with such functions in traditional medicine, thirty-nine of which have been subjected to pharmacological evaluations. Submicromolar antibacterial activities for several of these plants have been the driving force behind studies targeting their active constituents. This review accounts for close to a hundred of such entities, mainly isoquinoline alkaloids, which have been the focus in assays of thirty different bacterial pathogens. Promising activities were detected in several instances, although disappointingly the submicromolar level could not be breached. Also considered are structure–activity relationships which have emerged within the various groups of Amaryllidaceae alkaloids. [ABSTRACT FROM AUTHOR]

Background: Viral-borne diseases are amongst the oldest diseases known to mankind. They are responsible for some of the most ravaging effects wrought on human health and well-being. The use of plants against these ailments is entrenched in both traditional and secular medicine around the globe. Their natural abundance and chemical diversity have also boosted their appeal in drug discovery.Aim: The plant family Amaryllidaceae is distinguished for its alkaloid principles, some of which are of considerable interest in the clinical arena. This account is the outcome of a literature review undertaken to establish the applicability of these substances as antiviral agents.Methods: The survey utilized the search engines Google Scholar, PubMed, SciFinder, Scopus and Web of Science engaging the word 'antiviral' in conjunction with 'Amaryllidaceae' and 'Amaryllidaceae alkaloid'. The search returned over five hundred hits, of which around eighty were of relevance to the theme of the text.Results: Over eighty isoquinoline alkaloids have been screened against nearly fifty pathogens from fourteen viral families, the majority of which were RNA viruses. Potent activities were reported in some instances, such as that of trans-dihydronarciclasine against Yellow fever virus (IC50 0.003 μg/ml), with minimal effects being manifested on host cells. There were also promising results obtained from in vivo studies, in most cases without lethal effects on test subjects. Structure-activity relationship studies afforded useful insight to the antiviral pharmacophore, with the phenanthridone alkaloid nucleus shown to be the most enabling. Although the mechanistic basis to these activities pertained mostly to inhibition of DNA, RNA and protein synthesis, evidence was also forthcoming about the inhibitory action of some of the alkaloids against viral neuraminidase, protease and reverse transcriptase. In silico methods of analysis have offered further perspectives of how some of the alkaloids interact at the active sites of their targets.Conclusion: The Amaryllidaceae offers a viable platform for plant-based antiviral drug discovery. Its cause is strengthened not only by its wide proliferation and exploitation of its members in alternative forms of medicine, but also by its rich chemical diversity which has already spawned useful antiviral drug leads. [ABSTRACT FROM AUTHOR]

Feature extraction from a part model and Computer Numerical Control (CNC) code generation for machine tool control are the two extreme activities of a typical CAPP system. The present work discusses about a new methodology for automatic part feature extraction and CNC code generation for the invention of micro features in tool based micromachining processes. It has two main components; the first one deals with Extensible Mark-up Language (XML) based feature extraction from feature based model and interactive feature recognition. The second one deals with autonomous CNC code generation based on manufacturing features using various mathematical logic. Feature extraction through XML files avoids complex feature extraction process and automation of CNC code generation avoids human expertise and compatibility issues. The developed system integrated with micromachine tool through RS 232 communication interface. Hence for the given micro features, CNC code generation take place automatically and transferred to the micromachine tool in online with minimal user interface. The application of the proposed system verified with a case study. The developed system is limited to the parts having micro external step and drill features. Incorporation of more micro features, consideration of various other process planning activities and its part program generation ensures a complete CAPP system for micromachining. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated the parameter optimization of end milling operation for Inconel 718 super alloy with multi-response criteria based on the taguchi orthogonal array with the grey relational analysis. Nine experimental runs based on an L9 orthogonal array of Taguchi method were performed. Cutting speed, feed rate and depth of cut are optimized with considerations of multiple performance characteristics namely surface roughness and material removal rate. A grey relational grade obtained from the grey relational analysis is used to solve the end milling process with the multiple performance characteristics. Additionally, the analysis of variance (ANOVA) is also applied to identify the most significant factor. Finally, confirmation tests were performed to make a comparison between the experimental results and developed model. Experimental results have shown that machining performance in the end milling process can be improved effectively through this approach. [Copyright &y& Elsevier]

Abstract: Several of the Amaryllidaceae alkaloids are known for their cytotoxic properties, of which the lycorine group representatives are prominent for potent and cell line specific antiproliferative activities. As a distinct niche within the lycorine group, the phenanthridones, exemplified by narciclasine and pancratistatin, have shown much promise as remarkably selective cytotoxic agents and are presently at various stages of development, with a clinical candidate likely to appear on the market within the next decade. The crinane group of the Amaryllidaceae has also spawned several molecules, such as crinamine and haemanthamine, with promising cytotoxic activities. In the present study, the β-crinane distichamine as well as the phenanthridone narciprimine, both rare constituents of the Amaryllidaceae, are revealed as novel antiproliferative agents. Apoptosis-inducing effects are demonstrated for distichamine in human acute lymphoblastic leukemia (CEM) cells. These findings provide further insights to the structural details of the apoptosis-inducing pharmacophores resident within both series of alkaloids. [Copyright &y& Elsevier]

Abstract: Cycads are a group of slow-growing, perennial, dioecious plants which in geological times thrived during the Mesozoic era. The present worldwide complement of around 300 species is distributed through both tropical and subtropical regions of the globe, and has pronounced centres in Australia, Mexico and South Africa. These popular plants are known for their ornamental, economic, dietary and medicinal value. However, increased demand collectively from this sector, as well as decimation of large tracts of cycad populations in the wild through habitat destruction and unscrupulous collection, has precipitated a fragile conservation status for the family, with majority of its species listed as threatened by statutory bodies such as CITES and IUCN. Despite their popularity, cycads have for several centuries been known to be toxic. The plants have been shown to have carcinogenic, mutagenic, teratogenic and neurotoxic properties, and its major constituent principles macrozamin and cycasin have exhibited similar effects in model studies. Cycads are used widely in traditional medicine (TM) in South Africa and the majority of endemic species are commonly traded on local TM markets. The present study deals with the isolation of macrozamin from seed kernels of Encephalartos transvenosus and quantification of this toxic methylazoxymethanol (MAM) glycoside via HPLC in selected indigenous species. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Boophone disticha (Amaryllidaceae) is one of the most common bulbous plants used for medicinal purposes by the indigenous people of southern Africa. Its use as a narcotic substance by the Khoi/San tribes has been known for several centuries, while the Sotho, Xhosa and Zulu people are known to use the plant to treat a host of ailments, including inflammation, wounds, gynaecological conditions and psychosis. Aim of the study: Much of the pharmacological work on the plant, such as affinity to the serotonin transporter, has been based on its reputed usage for narcotic purposes. However, its widespread use to treat wounds and infections has not been linked to a specific chemical entity. In this regard, Boophone disticha was here examined for its phytochemical composition which could shed light on the use of the plant for such purposes. Materials and methods: The known crinane alkaloids buphanidrine and distichamine were isolated via column chromatography of the ethanolic extract of bulbs of Boophone disticha. Structural details of the compounds were determined by high field 2D NMR and mass spectroscopic techniques. Microbial activity against selected Gram-positive and Gram-negative bacteria was ascertained according to the micro-dilution assay. Results: Both buphanidrine and distichamine were uncovered as novel, broad spectrum moderately active, antibacterial agents with the best MIC value detected at 0.063mg/ml for Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. MIC values for Bacillus subtilis were two-fold less than that observed for the other three bacteria, suggesting that the extract and pure compounds were selective in their interaction with the bacterial pathogens. Conclusion: Phytochemical investigation of Boophone disticha has led to the identification of two known crinanes, buphanidrine and distichamine. Based on the reputed traditional use of the plant for wounds and infections, both compounds were screened for antibacterial activity which revealed them to be novel, broad spectrum antibacterial agents with the best MIC value set at 0.063mg/ml. Their close structural similarity may have bearing on their similar activity profiles. [ABSTRACT FROM AUTHOR]

Abstract: The discovery of a novel five-component 1,2,3-triazole-containing pharmacophore that exhibits potent and selective inhibition of aromatase (CYP 450 19A1) is described. All compounds are derived from an initial aldol reaction of a phenylacetate derivative with an aromatic aldehyde. Structure–activity data generated from both syn- and anti-aldol adducts provides initial insights into the requirements for both potency and selectivity. [Copyright &y& Elsevier]

Abstract: 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 (IC50 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: This work presents the results of an experimental investigation concerning the low-velocity impact behavior of woven glass fiber epoxy matrix composite laminates. Experimental test were performed according to ASTM standards using an instrumented falling weight impact testing machine. Impact test were conducted to characterize the type and extent of the damage observed in laminate for range of thickness subjected to different impact velocities. Correlation of the residual indentation of the impacted specimens provides a criterion for the extent of the damage. As the impact energy was increased, the samples experienced one of two types of damages: a crack from the center of the laminate to the edge, or significant damage consisting of a dent localized in the region of impact. The history of relevant kinematical, dynamic and energetic quantities, both to synthesize the dependency of the energy parameters and force threshold values on the impact velocity are discussed. [Copyright &y& Elsevier]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: The watershed characterization and modeling system (WCMS) was developed to support decision making and the management of water resources at a statewide level in West Virginia. Specific hydrological analysis functions were combined within a customized GIS interface to provide decision support capabilities to both technical and non-technical users. Components of the current system include: an overland flow path model that indicates optimum water quality sampling locations, flow estimation for all streams in an identified area, an instream water quality and loading model for pollutant levels, and a ranking model to prioritize treatment alternatives based on user defined criteria and preferences. The primary goals of this system are to provide consistent technical information related to natural watershed processes and to predict the impacts of alternative management scenarios for decision makers. WCMS is currently used by the West Virginia Department of Environmental Protection (WVDEP) to guide policy development and management decisions that address watershed and water quality issues throughout the state. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: An investigation of the constituents in heartwood and resin of Prunus avium is reported. A mini-library of structurally diverse flavanones and flavones was screened for human cytochrome P450 1A1, 3A4 and 19 (aromatase) inhibition, and for antifungal activity against a panel of pathogenic fungi. The defensive role of these natural plant flavonoids as antifungal phytoalexins and phytoanticipins is discussed. [Copyright &y& Elsevier]

Abstract: Two total syntheses of fully functionalized seco-analogs of the anticancer compound pancratistatin are reported. Structure–activity relationship (SAR) studies identified potent and selective inhibitors of human cytochrome P450 3A4 (CYP3A4) and revealed several core pharmacophoric elements. These studies identify potential roadblocks and will guide the further development of a viable selective clinical pancratistatin derivative. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: The selective apoptosis-inducing activity of Amaryllidaceae alkaloids belonging to the crinane-type is reported. A mini-library of natural and synthetic crinane alkaloids was assembled. Biological screening indicated crinamine 4 and haemanthamine 9 to be potent inducers of apoptosis in tumour cells at micromolar concentrations. Structure-activity relationships demonstrated the requirement for both an alpha-C2 bridge and a free hydroxyl at the C-11 position as pharmacophoric requirements for this activity. [Copyright &y& Elsevier]

Abstract: 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)Å 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, P n Bu3, P(O–2,4- t Bu2–Ph)3) the following electron donating ability series was established: L1 ∼L2 ∼P n Bu3 >PPh3 >P(O–2,4- t Bu2–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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Background: Fungal pathogenesis continues to be a burden to healthcare structures in both developed and developing nations. The gradual and irreversible loss of efficacies of existing antifungal medicines as well as the emergence of drug-resistant strains have contributed largely to this scenario. There is therefore a pressing need for new drugs from diverse structural backgrounds with improved potencies and novel modes of action to fortify or replace contemporary antifungal schedules.Aim: Alkaloids of the plant family Amaryllidaceae exhibit good growth inhibitory activities against several fungal pathogens. This review focuses on the mechanistic aspects of these antifungal activities. It achieves this by highlighting the molecular targets as well as structural features of Amaryllidaceae constituents which serve to enhance such action.Methods: During the information gathering stage extensive use was made of the three database platforms; Google Scholar, SciFinder and Scopus. In most instances articles were accessed directly from journals licensed to the University of KwaZulu-Natal. In the absence of such proprietary agreements the respective corresponding authors were approached directly for copies of papers.Results: Although several classes of molecules from the Amaryllidaceae have been probed for their antifungal effects, it is the key constituents lycorine and narciclasine which have together afforded the most profound mechanistic insights. These may be summarized as follows: (i) effects on the fungal cell wall and cell membrane; (ii) effects on morphology such as budding and hyphal growth; (iii) effects on fungal organelles such as ribosomes; (iv) effects on macromolecules such as DNA, RNA and proteins and; (v) identification of the active sites for these constituents.Conclusion: The key feature in the antifungal effects of Amaryllidaceae alkaloids is the inhibition of protein synthesis. This involved the inhibition of peptide bond formation by binding to yeast ribosomes via the 60S subunit. Related effects involved the inhibition of both DNA and RNA synthesis. These adverse effects were reflected morphologically on both the fungal cell wall and cell membrane. Such observations should prove useful in the chemotherapeutic arena should efforts shift towards the development of a clinical candidate. [ABSTRACT FROM AUTHOR]

Protozoan-borne diseases are prominent amongst diseases caused by parasites. Given their alarming morbidity and mortality statistics, there is ever growing interest in new therapies against these diseases. Whilst synthetic drugs such as benznidazole and melarsoprol have had a profound influence on the clinical setup, there has been significant interest in the phytochemical platform to also deliver such drug candidates. The plant family Amaryllidaceae is recognizable for its isoquinoline alkaloids, which exhibit attractive molecular architectures and interesting biological properties. This survey focuses on the antiprotozoal activities of 73 of such substances described in 18 different species of the Amaryllidaceae. Of these, 2- O -acetyllycorine was identified as the most potent (IC 50 0.15 μg/mL against Trypansoma brucei brucei). Also considered are structure-activity relationships which have served to modulate activities, as well as the plausible mechanisms that underpin these effects and afford insight to the Amaryllidaceae alkaloid antiprotozoal pharmacophore. [ABSTRACT FROM AUTHOR]

Abstract: This study offers a unique contribution to the literature by investigating the influential factors of energy-related, carbon dioxide emission intensity among a panel of 30 provinces in China covering the period 1991–2010. We use novel spatial panel data models to analyze the drivers of energy-related emission intensity, which we posit are characterized by spatial dependence. Our results suggest (1) emission intensities are negatively affected by per-capita, province-level GDP and population density; (2) emission intensities are positively affected by the structure of energy consumption and the transportation sector; and, (3) energy prices have no effect on emission intensities. [Copyright &y& Elsevier]

Abstract: A general, high yielding procedure is described for the esterification of carboxylic acids through carboxylate alkylation in phosphonium salt ionic liquid. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Characteristics of buildings and land cover surrounding buildings influence the number of bird-window collisions, yet little is known about whether bird-window collisions are associated with urbanization at large spatial scales. We initiated a continent-wide study in North America to assess how bird-window collision mortality is influenced by building characteristics, landscaping around buildings, and regional urbanization. In autumn 2014, researchers at 40 sites (N = 281 buildings) used standardized protocols to document collision mortality of birds, evaluate building characteristics, and measure local land cover and regional urbanization. Overall, 324 bird carcasses were observed (range = 0–34 per site) representing 71 species. Consistent with previous studies, we found that building size had a strong positive effect on bird-window collision mortality, but the strength of the effect on mortality depended on regional urbanization. The positive relationship between collision mortality and building size was greatest at large buildings in regions of low urbanization, locally extensive lawns, and low-density structures. Collision mortality was consistently low for small buildings, regardless of large-scale urbanization. The mechanisms shaping broad-scale variation in collision mortality during seasonal migration may be related to habitat selection at a hierarchy of scales and behavioral divergence between urban and rural bird populations. These results suggest that collision prevention measures should be prioritized at large buildings in regions of low urbanization throughout North America. [ABSTRACT FROM AUTHOR]

Highlights: [•] Twenty-three alkaloids were identified in Hippeastrum aulicum and H. calyptratum. [•] X-ray and CD analysis confirmed that aulicine (1) is a crinine-type alkaloid. [•] CD analysis verified 3-O-methyl-epimacowine (2) as a crinine-type alkaloid. [•] Correct 1D and 2D NMR spectral data were assigned for the alkaloid 11-oxohaemanthamine (3). [•] Complete NMR data are presented for some trimethoxyaryl homolycorine-type alkaloids. [Copyright &y& Elsevier]

Abstract: Bioisosteric replacement of cyclic ketone functionality with aryl halides was investigated on a centrally-flexible, five-component 1,2,3-triazole-containing pharmacophore, resulting in enhanced inhibition of aromatase (CYP450 19A1). Structure–activity data generated from both syn- and anti-aldol precursors provides significant insights into the requirements for enhanced potency, validating this novel ketone-to-aryl halide bioisostere hypothesis. [Copyright &y& Elsevier]

Growing economic crisis and strict government policies and regulations regarding the environment have forced the battery industries to practice the recycling process for both economic and environmental benefits. Moreover the consideration of sustainability issues makes the recycling process more significant, successful implementation of recycling activity in the battery industry requires several strategic decisions. Among these decisions, a complex decision faced by the management is to identify the suitable location for the establishment of a formal Battery Recycling Plant (BRP). In this research work, a three-stage hybrid methodology with the combination of ISM (Interpretive Structural Modeling), fuzzy AHP (Analytic Hierarchy Process), and fuzzy COPRAS (Complex Proportional Assessment of Alternatives) methods was proposed to select the best sustainable location from the available options for BRP in India. In this study, a total of eight experts were selected from both academia and industry. Initially in this paper, 4 main sustainable criteria and 20 sustainable sub-criteria were considered from the literature review and field visits along with experts' opinions for evaluation of alternatives. This work contains three stages. In the first stage, the ISM method was used to filter 18 important sustainable sub-criteria from the primary list of 20 sub-criteria, based on its higher driving power. Then, fuzzy AHP was applied in the second stage to compute the criteria weights. In the last stage, the fuzzy COPRAS was used to rank and choose the best sustainable location for BRP. The findings emphasize that the Environmental protection level, Distance from residential areas, Distance from water source, Capital investment, Government policies, Social acceptance, Availability of scrap batteries, and Availability of utilities were the most significant criteria in the sustainability dimension. Thus, the present work helps the management in the selection of an appropriate sustainable location for BRP. [Display omitted] • A hybrid methodology was proposed for selecting battery recycling plant location. • Sustainable criteria are considered for decision making. • Interpretive Structural Modeling was used to identify the noteworthy criteria. • Fuzzy Analytic Hierarchy Process was applied to obtain the criteria weights. • Fuzzy Complex Proportional Assessment of Alternatives was used to select location. [ABSTRACT FROM AUTHOR]