195 results on '"Jerald, J."'
Search Results
2. Chemical and biological studies of the South African Amaryllidaceae genera Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia
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Jerald J. Nair and Johannes Van Staden
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biology ,Phytochemical ,Traditional medicine ,Ammocharis ,Narciclasine ,Crinum ,Plant Science ,Amaryllidaceae ,Brunsvigia ,biology.organism_classification ,Amaryllis ,Cyrtanthus - Abstract
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.
- Published
- 2021
3. The plant family Amaryllidaceae as a source of cytotoxic homolycorine alkaloid principles
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Johannes Van Staden and Jerald J. Nair
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0106 biological sciences ,biology ,Alkaloid ,Topoisomerase ,Plant Science ,Homolycorine ,Pharmacology ,Lycorine ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,chemistry ,biology.protein ,Efflux ,Isoquinoline ,Pharmacophore ,Cytotoxicity ,010606 plant biology & botany - Abstract
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.
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- 2021
4. The Amaryllidaceae, a chemically and biologically privileged plant family
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Johannes Van Staden and Jerald J. Nair
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Botany ,Plant Science ,Amaryllidaceae ,Biology ,biology.organism_classification - Published
- 2021
5. Cytotoxic tazettine alkaloids of the plant family Amaryllidaceae
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Johannes Van Staden and Jerald J. Nair
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0106 biological sciences ,biology ,Alkaloid ,Plant Science ,Amaryllidaceae ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,Vinblastine ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Biochemistry ,chemistry ,medicine ,heterocyclic compounds ,Efflux ,Isoquinoline ,Cytotoxicity ,Amaryllidaceae Alkaloids ,Camptothecin ,010606 plant biology & botany ,medicine.drug - Abstract
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 (ED50 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.
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- 2021
6. Identification of Amaryllidaceae alkaloids in larvae of the ‘lily borer’ moth Brithys crini
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J. Van Staden, H.B. Papenfus, Dan Staerk, A.L. Andresen, and Jerald J. Nair
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Larva ,food.ingredient ,biology ,media_common.quotation_subject ,fungi ,Plant Science ,Insect ,Amaryllidaceae ,biology.organism_classification ,medicine.disease_cause ,Predation ,food ,Crinum moorei ,Brithys crini ,Botany ,Infestation ,medicine ,Amaryllidaceae Alkaloids ,media_common - Abstract
There are subtle mechanisms at work in nature to maintain a balance in the interactions between plants and animals. The production of secondary metabolites is one of the key strategies utilized by plants to minimize their over-exploitation. The ‘lily borer’ moth Brithys crini poses a considerable challenge to Amaryllidaceae plants owing to the devestation it can cause during the larval stage of its development. This, despite the fact that the Amaryllidaceae is richly endowed with an assortment of isoquinoline alkaloid constituents which exhibit a diverse array of biological properties, particularly cytotoxicity-related effects. In this study, laboratory-maintained larvae of B. crini were periodically fed fresh leaves of Crinum moorei during the September to November infestation period in Pietermaritzburg, South Africa. Solvent extracts of the plant leaves, moth larvae and larvae excrement material were then prepared and subjected to HPLC and LC–MS analyses. The presence of several alkaloids, including cherylline and ambelline, in all three extracts was ratified via HR-MS and NMR analyses. The identification of ambelline is noteworthy since it has not been reported in previous studies of C. moorei. Toxicity related criteria are also considered based on the present detection of alkaloids in B. crini larvae material, as well as precedence for their association with other known insect predators of the Amaryllidaceae.
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- 2020
7. Antiplasmodial constituents in the minor alkaloid groups of the Amaryllidaceae
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J. Van Staden and Jerald J. Nair
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0106 biological sciences ,Traditional medicine ,Alkaloid ,Mortality statistics ,Plant Science ,Minor (academic) ,Amaryllidaceae ,Biology ,medicine.disease ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Biological property ,medicine ,Malaria ,010606 plant biology & botany - Abstract
Malaria is responsible for majority of the morbidity and mortality statistics reflected by tropical diseases. Whilst effectively managed in most parts of the globe, it remains a scourge on the African continent where most cases of the disease are diagnosed annually. Plants have played a leading role as a source of malarial drugs which continue to dominate the clinical landscape today. Most if not all of these discoveries have as their basis evidence which can be traced back to traditional medicine. There is likewise precedence for the use of Amaryllidaceae plants in traditional medicinal approaches towards malaria. The chief phytochemical principles of the Amaryllidaceae are its isoquinoline alkaloids which are responsible for its diverse biological properties. These alkaloids may be divided into major and minor groups based on their distinguishing structural features as well as their natural abundance and distribution in the family. Whilst much has been written about the biological and chemical properties of the major alkaloid groups of the Amaryllidaceae, relatively little is known or understood about its minor alkaloid groups. This review focuses on the antiplasmodial activities described in the literature for the minor alkaloid group members of the Amaryllidaceae against various strains of the malarial pathogen Plasmodium falciparum . Three database platforms (Google Scholar, SciFinder and Scopus) were utilized for the literature search. Articles were accessed from journals licensed to the University of KwaZulu-Natal, or directly via the respective corresponding authors. Also considered are structural elements of these alkaloids which may be used to explain such activities as well as to provide a foundation in attempts to modulate activities. In addition, evidence is provided on the molecular basis to these effects which could guide efforts in drug discovery.
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- 2019
8. Caspase-inducing effects of lycorane and crinane alkaloids of the Amaryllidaceae
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J. Van Staden and Jerald J. Nair
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0106 biological sciences ,Programmed cell death ,biology ,Drug discovery ,Proteolytic enzymes ,Plant Science ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Apoptosis ,Cancer cell ,Cancer research ,biology.protein ,Cytotoxicity ,Amaryllidaceae Alkaloids ,Caspase ,010606 plant biology & botany - Abstract
Cancer is a leading cause of death worldwide. This, in spite of the tremendous gains made in cancer chemotherapies over the past several decades. The identification and development of new targets with greater structural diversities and better potencies are at the forefront of drug discovery endeavors across disciplines. Plants have afforded a significant number of successful anticancer drugs, several of which manifest their activities by inducing apoptosis (or programmed cell death) in cancer cells. The Amaryllidaceae alkaloids have similarly distinguished themselves as potent antiproliferative agents, some at the nanomolar level, with selective apoptosis inducing effects demonstrated in a wide variety of cancer cells. The proteolytic enzymes caspases are the key effectors of the apoptotic pathways, the main function of which is, in turn, the activation of caspases. Once activated caspases set in motion an intricately choreographed cascade of events leading to eventual cell death and phagocytosis. The lycorane and crinane group of alkaloids were amongst the first of the Amaryllidaceae for which apoptosis and attendant caspase inducing effects were discovered. These have been central in ongoing efforts to unravel the mechanistic basis to the cytotoxicity of these alkaloids. This review focuses on the various caspases which have been shown to be integral in apoptosis signaling pathways mediated by lycorane and crinane alkaloids.
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- 2019
9. Cytotoxic Agents in the Minor Alkaloid Groups of the Amaryllidaceae
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Jerald J. Nair and Johannes Van Staden
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Pharmaceutical Science ,Apoptosis ,01 natural sciences ,Analytical Chemistry ,Alkaloids ,Regular frequency ,Biological property ,Drug Discovery ,medicine ,heterocyclic compounds ,Amaryllidaceae Alkaloids ,Cytotoxicity ,Pharmacology ,biology ,010405 organic chemistry ,Cytotoxins ,Alkaloid ,Organic Chemistry ,Amaryllidaceae ,Cancer ,medicine.disease ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Biochemistry ,Cancer cell ,Molecular Medicine - Abstract
Over 600 alkaloids have to date been identified in the plant family Amaryllidaceae. These have been arranged into as many as 15 different groups based on their characteristic structural features. The vast majority of studies on the biological properties of Amaryllidaceae alkaloids have probed their anticancer potential. While most efforts have focused on the major alkaloid groups, the volume and diversity afforded by the minor alkaloid groups have promoted their usefulness as targets for cancer cell line screening purposes. This survey is an in-depth review of such activities described for around 90 representatives from 10 minor alkaloid groups of the Amaryllidaceae. These have been evaluated against over 60 cell lines categorized into 18 different types of cancer. The montanine and cripowellin groups were identified as the most potent, with some in the latter demonstrating low nanomolar level antiproliferative activities. Despite their challenging molecular architectures, the minor alkaloid groups have allowed for facile adjustments to be made to their structures, thereby altering the size, geometry, and electronics of the targets available for structure-activity relationship studies. Nevertheless, it was seen with a regular frequency that the parent alkaloids were better cytotoxic agents than the corresponding semisynthetic derivatives. There has also been significant interest in how the minor alkaloid groups manifest their effects in cancer cells. Among the various targets and pathways in which they were seen to mediate, their ability to induce apoptosis in cancer cells is most appealing.
- Published
- 2021
10. Correlates of bird collisions with buildings across three North American countries
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John E. Quinn, Stephen B. Hager, Terri J. Maness, Amber M. Roth, Michelle L. Anderson, Natasha D. G. Hagemeyer, Elizabeth A. Lago, Rebecca I. Cooper, Jessa M. Madosky, Rubén Ortega-Álvarez, Robert L. Curry, Scott R. Loss, Michael W. Butler, Nicolette L. Cagle, Kristine N. Hopfensperger, Jerald J. Dosch, Matthew Simmons, Lindsey A. Walters, Amber L. Pitt, Eric L. Walters, Daniel Klem, Eric M. Butler, Ryan T. Schmitz, Bradley J. Cosentino, Ally S. Lahey, Aura Puga-Caballero, Rafael Calderón-Parra, Erin E. Fraser, Kelly J. McKay, Ross A. Furbush, Corey S. Riding, Angelo P. Capparella, Craig S. Machtans, Than J. Boves, Anqi Chen, Claire W. Varian-Ramos, Karen Dyson, Natalia Ocampo-Peñuela, Kendra Cipollini, Jesse Vigliotti, Kathy Winnett-Murray, Iriana Zuria, David Brandes, Jared A. Elmore, Thomas A. Contreras, Marja H. Bakermans, Sean B. Menke, Jason T. Weir, Jaclyn L. Schnurr, Alexis D. Smith, Clay E. Corbin, Timothy J. O'Connell, and April A.T. Conkey
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0106 biological sciences ,Canada ,Conservation of Natural Resources ,010603 evolutionary biology ,01 natural sciences ,Warbler ,Songbirds ,Abundance (ecology) ,Animals ,Catharus ,Mexico ,Ecology, Evolution, Behavior and Systematics ,Nature and Landscape Conservation ,Ecology ,biology ,Sitta carolinensis ,010604 marine biology & hydrobiology ,Sampling (statistics) ,Insectivore ,Vegetation ,biology.organism_classification ,United States ,Geography ,North America ,Nuthatch - Abstract
Collisions with buildings cause up to 1 billion bird fatalities annually in the United States and Canada. However, efforts to reduce collisions would benefit from studies conducted at large spatial scales across multiple study sites with standardized methods and consideration of species- and life-history-related variation and correlates of collisions. We addressed these research needs through coordinated collection of data on bird collisions with buildings at sites in the United States (35), Canada (3), and Mexico (2). We collected all carcasses and identified species. After removing records for unidentified carcasses, species lacking distribution-wide population estimates, and species with distributions overlapping fewer than 10 sites, we retained 269 carcasses of 64 species for analysis. We estimated collision vulnerability for 40 bird species with ≥2 fatalities based on their North American population abundance, distribution overlap in study sites, and sampling effort. Of 10 species we identified as most vulnerable to collisions, some have been identified previously (e.g., Black-throated Blue Warbler [Setophaga caerulescens]), whereas others emerged for the first time (e.g., White-breasted Nuthatch [Sitta carolinensis]), possibly because we used a more standardized sampling approach than past studies. Building size and glass area were positively associated with number of collisions for 5 of 8 species with enough observations to analyze independently. Vegetation around buildings influenced collisions for only 1 of those 8 species (Swainson's Thrush [Catharus ustulatus]). Life history predicted collisions; numbers of collisions were greatest for migratory, insectivorous, and woodland-inhabiting species. Our results provide new insight into the species most vulnerable to building collisions, making them potentially in greatest need of conservation attention to reduce collisions and into species- and life-history-related variation and correlates of building collisions, information that can help refine collision management.Correlaciones de las Colisiones de Aves contra Edificios en Tres Países de América del Norte Resumen Las colisiones contra los edificios causan hasta mil millones de fatalidades de aves al año en los Estados Unidos y en Canadá. Sin embargo, los esfuerzos por reducir estas colisiones se beneficiarían con estudios realizados a grandes escalas espaciales en varios sitios de estudio con métodos estandarizados y considerando las variaciones relacionadas a la historia de vida y a la especie y las correlaciones de las colisiones. Abordamos estas necesidades de investigación por medio de una recolección coordinada de datos sobre las colisiones de aves contra edificios en los Estados Unidos (35), Canadá (3) y México (2). Recolectamos todos los cadáveres y los identificamos hasta especie. Después de retirar los registros de cadáveres no identificados, las especies sin estimaciones poblacionales a nivel distribución y las especies con distribuciones traslapadas en menos de diez sitios, nos quedamos con 269 cadáveres de 64 especies para el análisis. Estimamos la vulnerabilidad a colisiones para 40 especies con ≥2 fatalidades con base en la abundancia poblacional para América del Norte, el traslape de su distribución entre los sitios de estudio y el esfuerzo de muestreo. De las diez especies que identificamos como las más vulnerables a las colisiones, algunas han sido identificadas previamente (Setophaga caerulescens), y otras aparecieron por primera vez (Sitta carolinensis), posiblemente debido a que usamos una estrategia de muestreo más estandarizada que en los estudios previos. El tamaño del edificio y el área del vidrio estuvieron asociados positivamente con el número de colisiones para cinco de ocho especies con suficientes observaciones para ser analizadas independientemente. La vegetación alrededor de los edificios influyó sobre las colisiones solamente para una de esas ocho especies Catharus ustulatus). Las historias de vida pronosticaron las colisiones; el número de colisiones fue mayor para las especies migratorias, insectívoras y aquellas que habitan en las zonas boscosas. Nuestros resultados proporcionan una nueva perspectiva hacia las especies más vulnerables a las colisiones contra edificios, lo que las pone en una necesidad potencialmente mayor de atención conservacionista para reducir estas colisiones y de estudio de las variaciones relacionadas con la especie y la historia de vida y las correlaciones de las colisiones contra edificios, información que puede ayudar a refinar el manejo de colisiones.在美国和加拿大, 每年有多达10亿只鸟类死于撞击建筑物。在大空间尺度上跨多个研究地点、采用标准化方法, 并考虑鸟类物种及生活史变异和其它撞击相关因素的研究, 将有助于减少鸟类与建筑物的碰撞。本研究通过整理收集美国、加拿大和墨西哥多个位点 (数量分别为 35 个、3 个和 2 个) 鸟类撞击建筑物的数据来满足以上的研究需求。我们首先收集了所有鸟类尸体并进行物种鉴定。在排除掉不能辨认的尸体、缺少分布范围内种群估计数据的物种、分布区与少于 10 个位点有重叠的物种后, 我们保留了 64 个物种的 269 个死亡事件进行分析。我们根据鸟类的北美种群数量、分布区与研究位点的重叠情况和抽样工作量, 估计了死亡个体≥2 只的 40 种鸟类的撞击脆弱性。本研究确定了最易发生撞击的 10 个物种, 其中包括已经被以往研究提及的物种 (如黑喉蓝林莺 [Setophaga caerulescens]) , 也有首次报道的物种 (如白胸鳾 [Sitta carolinensis]), 这可能是因为我们使用了比以往研究更注重标准化的抽样方法。在有足够观察数据以支持独立分析的 8 个物种中, 有 5 个物种的撞击次数与建筑大小和玻璃面积呈正相关;只有1个物种 (斯氏夜鸫 [Catharus ustulatus]) 的撞击受到建筑物周围植被的影响。生活史也可以预测撞击情况:迁徙鸟类、食虫鸟类和林栖鸟类的撞击次数最多。我们的研究结果为最易发生建筑物撞击伤害的鸟类物种提供了新的见解, 这些物种可能最需要保护以减少撞击, 本研究还深入探究了鸟类物种及生活史变异和其它撞击相关因素, 这些信息有助于改进鸟类撞击管理。【翻译: 胡怡思; 审校: 聂永刚】.
- Published
- 2020
11. Effects of urbanization on the population structure of freshwater turtles across the United States
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Erin S. Lindquist, Sandra L. Cooke, Kristen S. Genet, Jerald J. Dosch, Bradley J. Cosentino, Patrick W. Crumrine, Laurel J. Anderson, Craig R. Zimmermann, Madeline N. Santulli, K. Greg Murray, David R. Bowne, Peter D. Smallwood, Jason W. Dallas, Alexandra Doran, Rebecca A. Urban, Frank T. Kuserk, Daniel L. Druckenbrod, Peter A. Kish, Kathy Winnett-Murray, Timothy J. Muir, Carol Mankiewicz, Todd S. Fredericksen, Danielle Garneau, James G. March, Richard D. Durtsche, Frank J. Sicignano, Christopher P. Bloch, and Mary Beth Kolozsvary
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0106 biological sciences ,Conservation of Natural Resources ,Population ,Wildlife ,Fresh Water ,010603 evolutionary biology ,01 natural sciences ,law.invention ,law ,Urbanization ,Animals ,Turtle (robot) ,education ,Predator ,Ecology, Evolution, Behavior and Systematics ,Nature and Landscape Conservation ,education.field_of_study ,Ecology ,biology ,010604 marine biology & hydrobiology ,biology.organism_classification ,United States ,Turtles ,Geography ,Spatial ecology ,Female ,Painted turtle ,Sex ratio - Abstract
Landscape-scale alterations that accompany urbanization may negatively affect the population structure of wildlife species such as freshwater turtles. Changes to nesting sites and higher mortality rates due to vehicular collisions and increased predator populations may particularly affect immature turtles and mature female turtles. We hypothesized that the proportions of adult female and immature turtles in a population will negatively correlate with landscape urbanization. As a collaborative effort of the Ecological Research as Education Network (EREN), we sampled freshwater turtle populations in 11 states across the central and eastern United States. Contrary to expectations, we found a significant positive relationship between proportions of mature female painted turtles (Chrysemys picta) and urbanization. We did not detect a relationship between urbanization and proportions of immature turtles. Urbanization may alter the thermal environment of nesting sites such that more females are produced as urbanization increases. Our approach of creating a collaborative network of scientists and students at undergraduate institutions proved valuable in terms of testing our hypothesis over a large spatial scale while also allowing students to gain hands-on experience in conservation science.
- Published
- 2018
12. Cytotoxic Phenanthridone Alkaloid Constituents of the Amaryllidaceae
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Johannes Van Staden and Jerald J. Nair
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Traditional medicine ,biology ,Chemistry ,Alkaloid ,Cytotoxic T cell ,Amaryllidaceae ,biology.organism_classification - Published
- 2019
13. Antiplasmodial Lycorane Alkaloid Principles of the Plant Family Amaryllidaceae
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Johannes Van Staden and Jerald J. Nair
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Antiparasitic ,medicine.drug_class ,Plasmodium falciparum ,Pharmaceutical Science ,01 natural sciences ,Analytical Chemistry ,chemistry.chemical_compound ,Antimalarials ,Structure-Activity Relationship ,Drug Discovery ,medicine ,Animals ,Humans ,Antimalarial Agent ,Artemisinin ,Pharmacology ,biology ,Traditional medicine ,010405 organic chemistry ,Drug discovery ,Alkaloid ,Organic Chemistry ,Amaryllidaceae ,Lycorine ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,chemistry ,Amaryllidaceae Alkaloids ,Molecular Medicine ,Pharmacophore ,medicine.drug - Abstract
The spread of malaria is thought to have followed human expansion out of Africa some 60 – 80 thousand years ago. With its prevalence in pantropical countries of the world and epicenter localized in Africa, malaria is now considered an unnecessary burden to overworked and under-resourced healthcare structures. Plants have long afforded a fertile hunting ground for the search and identification of structurally diverse antimalarial agents, such as quinine and artemisinin. This survey examines the antiparasitic properties of the family Amaryllidaceae via the antiplasmodial activities demonstrated for its lycorane alkaloid principles. Of these, 24 were natural compounds identified in 20 species from 11 genera of the Amaryllidaceae family, whilst the remaining 28 were synthetically derived entities based on the lycorane skeleton. These were screened against ten different strains of the malarial parasite Plasmodium falciparum, wherein the parent compound lycorine was shown to be the most potent with an IC50 of 0.029 µg/mL in the FCR-3 strain seen to be the best. Structure-activity relationship studies revealed that good activities were detectable across both the natural compounds as well as the synthetically accessed derivatives. Such studies also highlighted that there are several inherent structural features that define the lycorane alkaloid antiplasmodial pharmacophore, such as the nature of its ring systems and properties of its substituents. Mechanistically, a limited number of studies confirmed that lycorane alkaloids manifest their action by targeting enzymes associated with the plasmodial FAS-II biosynthetic pathways. Overall, these alkaloids have provided useful, convenient, and accessible scaffolds for antimalarial-based drug discovery.
- Published
- 2019
14. The Amaryllidaceae as a source of antiplasmodial crinane alkaloid constituents
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Jerald J. Nair and Johannes Van Staden
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Pharmacology ,Traditional medicine ,Molecular Structure ,Alkaloid ,Amaryllidaceae ,Phytochemicals ,Plasmodium falciparum ,Artemisia annua ,General Medicine ,Biology ,biology.organism_classification ,medicine.disease ,Antimalarials ,Drug Discovery ,medicine ,Amaryllidaceae Alkaloids ,Potency ,Pharmacophore ,Medicinal plants ,Malaria - Abstract
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 ED50 of 0.14 μg/mL (for augustine in the D-6 strain) and IC50 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.
- Published
- 2019
15. New Alkaloids fromHippeastrum papilio(R<scp>avenna</scp>) V<scp>an</scp>S<scp>cheepen</scp>
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Jean Paulo de Andrade, Luciana R. Tallini, Laura Torras-Claveria, José Angelo S. Zuanazzi, Warley de Souza Borges, Ying Guo, Jerald J. Nair, Jaume Bastida, Natalia B. Pigni, and Francesc Viladomat
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Stereochemistry ,Plant composition ,01 natural sciences ,Biochemistry ,Catalysis ,Ravenna ,Inorganic Chemistry ,Drug Discovery ,Botany ,PAPILINE ,Physical and Theoretical Chemistry ,Chemical composition ,HAEMANTHAMINE-3-O-(3-HYDROXYBUTANOYL) ,HOMOLYCORINE-TYPE DERIVATIVES ,biology ,010405 organic chemistry ,Chemistry ,HIPPEASTRUM PAPILIO ,Otras Ciencias Químicas ,Organic Chemistry ,Ciencias Químicas ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,ALKALOIDS ,Hippeastrum papilio ,CIENCIAS NATURALES Y EXACTAS ,HIPPAPILINE - Abstract
A new phytochemical study of the indigenous Brazilian species Hippeastrum papilio is reported herein. Three novel Amaryllidaceae alkaloids were isolated, including hippapiline (1), papiline (2), and 3-O-demethyl-3-O-(3-hydroxybutanoyl)haemanthamine (3). Their structures were determined by physical and spectroscopic methods. In addition, the known alkaloids, haemanthamine (4), galanthamine (5), narwedine (6), 11β-hydroxygalanthamine (7), apogalanthamine (8), and 9-O-demethyllycosinine B (9) were identified. The unusual cis-B/C-ring fusion for the new homolycorine representative hippapiline was ratified by NMR and CD spectroscopy. Fil: Guo, Ying. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España Fil: Andrade, Jean P. de. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España. Universidade Federal do Espírito Santo; Brasil Fil: Pigni, Natalia Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; Argentina. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España Fil: Torras-Claveria, Laura. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España. Universidade Federal do Espírito Santo; Brasil Fil: Tallini, Luciana R.. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España Fil: Souza Borges, Warley de. Universidade Federal do Espírito Santo; Brasil Fil: Viladomat, Francesc. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España Fil: Nair, Jerald J.. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España Fil: Zuanazzi, José A. S.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Bastida, Jaume. University of Barcelona. Faculty of Pharmacy. Department of Natural Products, Plant Biology and Soil Science; España
- Published
- 2016
16. Cell cycle modulatory effects of Amaryllidaceae alkaloids
- Author
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Jerald J. Nair and Johannes Van Staden
- Subjects
0301 basic medicine ,Cell ,Antineoplastic Agents ,Apoptosis ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Structure-Activity Relationship ,0302 clinical medicine ,Alkaloids ,Neoplasms ,medicine ,Cytotoxic T cell ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Mode of action ,Amaryllidaceae Alkaloids ,Cell Cycle ,General Medicine ,Cell Cycle Checkpoints ,Cell cycle ,Antineoplastic Agents, Phytogenic ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell - 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.
- Published
- 2018
17. Antifungal constituents of the plant family Amaryllidaceae
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Johannes Van Staden and Jerald J. Nair
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Pharmacology ,Antifungal ,Antifungal Agents ,Traditional medicine ,010405 organic chemistry ,medicine.drug_class ,Plant Extracts ,Amaryllidaceae ,Growth inhibitory ,Surgical procedures ,Biology ,biology.organism_classification ,Chemical basis ,01 natural sciences ,0104 chemical sciences ,Multiple drug resistance ,010404 medicinal & biomolecular chemistry ,Minimum inhibitory concentration ,medicine ,Humans - Abstract
Globalization, the modern lifestyle, immuno-suppressive agents, invasive surgical procedures, the loss of efficacies of existing drugs, and multidrug resistance are some of the factors used to explain the rise in fungal infections in recent years. Significant advances have been made in attempts to replace existing antifungal schedules, especially with synthetic targets. The identification of other platforms for drug discovery is now entrenched in research programs across the globe. Plants offer significant benefits owing to their numerical superiority, exceedingly broad chemical basis and appealing sustainability characteristics. Furthermore, plants have a long and rich historical association with traditional approaches towards fungal diseases. These have in numerous instances served as markers in the bioassay-guided identification of the active constituents. Although the plant family Amaryllidaceae is conventionally associated with cancer and motor-neuron disease chemotherapies, around 30 of its species have been examined for antifungal activities with microgram per millilitre inhibitory activities detected in several instances. This review focuses on the nearly 40 constituents from the family, mainly isoquinoline alkaloids, which have been screened against around 50 fungal pathogens. Encouragingly, microgram per millilitre growth inhibitory activities were applicable for several of the compounds with a minimum inhibitory concentration of 4 μg/ml seen to be the lowest.
- Published
- 2017
18. Little evidence of native and non-native species influencing one another's abundance and distribution in the herb layer of an oak woodland
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Amanda J. Wareham, Michael D. Anderson, Mark A. Davis, Lilly Bock‐Brownstein, Jerald J. Dosch, Anna Staudenmaier, and Melena Suliteanu
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Ecology ,Species diversity ,Introduced species ,Plant Science ,Woodland ,Alliaria petiolata ,Biology ,biology.organism_classification ,Invasive species ,Common species ,Abundance (ecology) ,Botany ,Species richness - Abstract
Question To what extent are species, including native and non-native species, influencing one another's distribution and abundance in the herb layer of a Minnesota oak woodland? Location Oak woodland succeeding into a more mesic forest, on bluffland of the Mississippi River, east-central Minnesota. Methods We collected plant composition and species cover data in 182 1.0 × 0.5 m quadrats regularly spaced on a 6-ha study grid in the oak woodland. We also recorded slope, slope position, aspect, elevation and photosynthetically active radiation (PAR) at each quadrat. Results Presence and abundance of other plant species, topographic variables and light availability explained only a small portion of the variation (5–19%) in the distribution and abundance of individual species. The most common strongest predictor of cover for the ten most common species was species richness, with the association being positive. The non-native species, garlic mustard (Alliaria petiolata) exhibited the strongest positive association with species richness. Only one of the 45 pair-wise comparisons of the ten species resulted in a negative relationship between the species. Abundance and distribution of two species were associated with topographic features, but this accounted for much less of the variation in abundance than did species richness. Conclusion We found little evidence that competition or any other interactions among common herb layer species, including the non-native Alliaria petiolata, play an important role in determining the abundance and the distribution of herb layer species in this oak woodland. Topographic factors may explain a small amount of the distribution and abundance patterns of a few species. But, for the most part, species are more likely to be present when other species are present, suggesting that they are simply establishing in microsites favourable to plants in general.
- Published
- 2015
19. Seasonal pharmacological properties and alkaloid content in Cyrtanthus contractus N.E. Br
- Author
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J.F. Finnie, J. Van Staden, Miroslav Strnad, Bhekumthetho Ncube, Jerald J. Nair, and Lucie Rárová
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biology ,Aché ,Alkaloid ,Biological activity ,Plant Science ,Amaryllidaceae ,Pharmacology ,Antimicrobial ,biology.organism_classification ,Acetylcholinesterase ,language.human_language ,Bulb ,Cyrtanthus ,chemistry.chemical_compound ,chemistry ,language - Abstract
Representatives of the genus Cyrtanthus including Cyrtanthus contractus of the Amaryllidaceae family are widely used in African traditional medicine for the treatment of a range of ailments, including mental illness and age-related dementia. The alkaloid constituents distributed within the genus, which are chiefly responsible for the biological activity of the derived extracts, are thought to be influenced by changes in the growing environment. Natural growing populations of C. contractus were tagged and collected every 15th day of each month over a 12 month period. The ethanol bulb extracts from each of the collected samples were evaluated for total alkaloid content, cytotoxic effects, acetylcholinesterase and cyclooxygenase inhibition as well as antimicrobial activities. Some notable bioactivities were recorded for extracts collected during certain months of the year, particularly the cytotoxic effects against human cancer cell lines and enzyme inhibition (AChE and COX). The cytotoxic effects and AChE and COX enzyme inhibitory activities of extracts collected in May and September are of considerable interest. Similarly total alkaloids varied markedly from one month to the other. The bioactivity exhibited by C. contractus bulb extracts during certain months of the year, particularly in May and September, justifies the collection and use of these bulbs for treatment of the relevant ailments in traditional medicine during these periods.
- Published
- 2015
20. Antibacterial constituents of the plant family Amaryllidaceae
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Anke Wilhelm, Johannes Van Staden, Jerald J. Nair, and Susanna L. Bonnet
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Antibiotic drug ,Clinical Biochemistry ,Pharmaceutical Science ,Biology ,Gram-Positive Bacteria ,01 natural sciences ,Biochemistry ,Alkaloids ,Drug Discovery ,Botany ,Gram-Negative Bacteria ,Amaryllidaceae Alkaloids ,Molecular Biology ,Traditional medicine ,010405 organic chemistry ,Plant Extracts ,Organic Chemistry ,Amaryllidaceae ,Antimicrobial ,biology.organism_classification ,0104 chemical sciences ,Anti-Bacterial Agents ,010404 medicinal & biomolecular chemistry ,Infectious disease (medical specialty) ,Molecular Medicine - Abstract
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.
- Published
- 2017
21. Population and plant community dynamics involving garlic mustard (Alliaria petiolata) in a Minnesota Oak Woodland: a four year study1
- Author
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Claire MacMillen, Yuris Martinez, Marta LeFevre-Levy, Nolan Kriegel, Michael D. Anderson, Stephen Tyndel, Jerald J. Dosch, Casey Dallavalle, and Mark A. Davis
- Subjects
education.field_of_study ,Ecology ,Population ,Plant community ,Plant Science ,Alliaria petiolata ,Woodland ,Biology ,Native plant ,biology.organism_classification ,Invasive species ,Plant ecology ,education ,Ecology, Evolution, Behavior and Systematics ,Woody plant - Abstract
Garlic mustard, Alliaria petiolata (M. Bieb.) Cavara & Grande, a European biennial, has become common in many Midwestern and eastern North American forests. Researchers have sometimes documented a two-year (two-point) population cycle in which the vegetative and reproductive phases alternate in abundance. However, little research has been conducted on the scale dependence of the two-point cycle and the extent to which the cycle is dependent on the density of A. petiolata. In addition to this interest in A. petiolata's population dynamics, researchers have investigated A. petiolata's effects on other plant species, often concluding that it displaces native herbs and inhibits tree seedling growth and survival through the production of allelochemicals. In order to examine both the population dynamics of A. petiolata and its possible effects on North American native plants, we conducted a four year study in which we monitored A. petiolata in a 6.2 ha portion of a Minnesota oak (Quercus) woodland at t...
- Published
- 2014
22. Pasture succession in the Neotropics: extending the nucleation hypothesis into a matrix discontinuity hypothesis
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Jerald J. Dosch, Walter P. Carson, and Chris J. Peterson
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Costa Rica ,Conservation of Natural Resources ,Tropical Climate ,Ecology ,Nucleation ,Ecological succession ,Vegetation ,Biology ,Graminoid ,Discontinuity (geotechnical engineering) ,Habitat ,Biological dispersal ,Regeneration (ecology) ,Ecosystem ,Ecology, Evolution, Behavior and Systematics - Abstract
The nucleation hypothesis appears to explain widespread patterns of succession in tropical pastures, specifically the tendency for isolated trees to promote woody species recruitment. Still, the nucleation hypothesis has usually been tested explicitly for only short durations and in some cases isolated trees fail to promote woody recruitment. Moreover, at times, nucleation occurs in other key habitat patches. Thus, we propose an extension, the matrix discontinuity hypothesis: woody colonization will occur in focal patches that function to mitigate the herbaceous vegetation effects, thus providing safe sites or regeneration niches. We tested predictions of the classical nucleation hypothesis, the matrix discontinuity hypothesis, and a distance from forest edge hypothesis, in five abandoned pastures in Costa Rica, across the first 11 years of succession. Our findings confirmed the matrix discontinuity hypothesis: specifically, rotting logs and steep slopes significantly enhanced woody colonization. Surprisingly, isolated trees did not consistently significantly enhance recruitment; only larger trees did so. Finally, woody recruitment consistently decreased with distance from forest. Our results as well as results from others suggest that the nucleation hypothesis needs to be broadened beyond its historical focus on isolated trees or patches; the matrix discontinuity hypothesis focuses attention on a suite of key patch types or microsites that promote woody species recruitment. We argue that any habitat discontinuities that ameliorate the inhibition by dense graminoid layers will be foci for recruitment. Such patches could easily be manipulated to speed the transition of pastures to closed canopy forests.
- Published
- 2014
23. Traditional usage, phytochemistry and pharmacology of the South African medicinal plant Boophone disticha (L.f.) Herb. (Amaryllidaceae)
- Author
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Jerald J. Nair and Johannes Van Staden
- Subjects
Pharmacology ,education.field_of_study ,food.ingredient ,Traditional medicine ,Boophone disticha ,Population ,Biology ,biology.organism_classification ,language.human_language ,Indigenous ,South Africa ,food ,Herb ,Drug Discovery ,Liliaceae ,language ,Humans ,Plant Preparations ,Xhosa ,African traditional medicine ,Cyclo-oxygenase ,Traditional knowledge ,education ,Phytotherapy - Abstract
Ethnopharmacological relevance Boophone disticha is the most common member of the South African Amaryllidaceae used extensively in traditional medicine of the various indigenous population groups, including the Sotho, Xhosa and Zulu as well as the San. This survey was carried out to identify and highlight areas relevant to the traditional usage of Boophone disticha. Pharmacological aspects were examined with the purpose of reconciling these with the traditional usage of the plant. In relation to phytochemical make-up, particular attention was paid on how its alkaloid constitution might corroborate the various biological effects manifested by the plant. Materials and methods Information gathering involved the use of four different database platforms, including Google Scholar, ScienceDirect, SciFinder® and Scopus. Arrangement and detailing of this information is as reflected in the various sections of the paper. Results Sixteen categories were identified under which Boophone disticha finds use in traditional medicine. These were shown to include general usage purposes, such as ‘cultural and dietary’, ‘well-being’, ‘personal injury’, ‘divinatory purposes’, ‘psychoactive properties’ and ‘veterinary uses’. Furthermore, traditional usage was seen to involve six body systems, including functions pertaining to the circulatory, gastrointestinal, muscular, neurological, respiratory and urinary systems. The four remaining categories relate to use for inflammatory conditions, cancer, malaria and tuberculosis. Overall, three areas were discernible in which Boophone disticha finds most usage, which are (i) ailments pertaining to the CNS, (ii) wounds and infections, and (iii) inflammatory conditions. In addition, several aspects pertaining to the toxic properties of the plant are discussed, including genotoxicity, mutagenicity and neurotoxicity. Conclusion The widespread ethnic usage of Boophone disticha has justified its standing as a flagship for the Amaryllidaceae and its relevance to South African traditional medicine. Furthermore, its promising pharmacological and phytochemical profiles have stimulated significant interest in the clinical realm, especially in the areas of cancer and motor neuron disease chemotherapy. These collective properties should prove useful in steering the progress of the plant towards a wider audience.
- Published
- 2014
24. Antiplasmodial Studies Within the Plant Family Amaryllidaceae
- Author
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Jerald J. Nair and Johannes Van Staden
- Subjects
Pharmacology ,Quinine ,biology ,Traditional medicine ,010405 organic chemistry ,First line ,food and beverages ,Plant Science ,General Medicine ,Amaryllidaceae ,medicine.disease ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,parasitic diseases ,Drug Discovery ,medicine ,Artemisinin ,Malaria ,medicine.drug - Abstract
Plants have long served as a first line of defense response to malaria. They have also spawned several classes of antimalarial drugs such as quinine and artemisinin. However, most if not all of these drugs have succumbed to multidrug resistance, thus reigniting interest in the identification of novel chemotherapies against this parasitic disease. The starting point for many of such endeavors lies with the plants themselves whose extracts have served as herbal remedies, which originate from traditional medicine (TM). Several species of the Amaryllidaceae have been shown to have such functions in TM. This survey examines those plants of the family, which have hitherto been examined for antiplasmodial effects against the malarial parasite Plasmodium falciparum. Also considered are the alkaloid constituents of these plants, which have demonstrated activities against various strains of the pathogen. Particular emphasis is made on those plants which both demonstrate such activity as well as have a place in traditional therapies for malaria.
- Published
- 2019
25. The Plant Family Amaryllidaceae: Special Collection Celebrating the 80th Birthday of Professor Johannes van Staden
- Author
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Jerald J. Nair
- Subjects
Pharmacology ,Complementary and alternative medicine ,biology ,media_common.quotation_subject ,Drug Discovery ,Plant Science ,General Medicine ,Art ,Amaryllidaceae ,biology.organism_classification ,Classics ,media_common - Published
- 2019
26. Comparison of the non‐native herbAlliaria petiolatawith dominant native herbs in microhabitats of a Midwestern forest
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Zach Moore, Jerald J. Dosch, Allison Pillar, Michael D. Anderson, Cody Dalrymple, Alex Lewanski, Mark A. Davis, Craig Burke, Mira W. Ensley-Field, Phuong Nguyen, Rina Morisawa, and Paul Manning
- Subjects
Herbivore ,food.ingredient ,Ecology ,Plant community ,Introduced species ,Alliaria petiolata ,Biology ,Native plant ,biology.organism_classification ,Plant ecology ,food ,Herb ,Forest ecology ,Ecology, Evolution, Behavior and Systematics - Published
- 2019
27. Phenanthridone Alkaloids of the Amaryllidaceae as Activators of the Apoptosis-related Proteolytic Enzymes, Caspases
- Author
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Johannes Van Staden and Jerald J. Nair
- Subjects
0301 basic medicine ,Pharmacology ,biology ,Chemistry ,Proteolytic enzymes ,Plant Science ,General Medicine ,Amaryllidaceae ,biology.organism_classification ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Complementary and alternative medicine ,Biochemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Drug Discovery ,biology.protein ,Caspase - Abstract
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.
- Published
- 2018
28. Antigonococcal activity of Ximenia caffra Sond. (Olacaceae) and identification of the active principle
- Author
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J.C. Chukwujekwu, J. Van Staden, F. R. Van Heerden, R.B. Mulaudzi, and Jerald J. Nair
- Subjects
Ximenia ,Ximenia caffra ,biology ,Traditional medicine ,Active principle ,Antigonococcal ,Plant Science ,Ascorbic acid ,biology.organism_classification ,medicine.disease_cause ,Neisseria gonorrhoeae ,Ethnobotany ,Botany ,medicine ,Bioassay ,Olacaceae ,Vomifoliol - Abstract
article i nfo The "large sour plum" tree Ximenia caffra Sond. (Olacaceae) is the only African representative of the genus Ximenia L., with a distribution covering East Africa, from Tanzania in the north to South Africa, as well as parts of Botswana and Namibia. It has many uses in traditional medicine, including treatment of wounds and infections as well as diarrhea, which have been verified through various pharmacological studies. Fur- thermore, the plant is also known for its nutritional and cosmetic value. Its edible fruits are known to be high in protein, potassium and vitamin C, while the seed oil, also referred to as "Ximenia oil" is rich in long chain unsaturated fatty acids and finds use as a domestic biofuel, with characteristics amenable to cosmetic development as topical applicants. Extracts of the plants are also widely used for treating sexually transmit- ted infections (STIs), which has been verified through ethnobotanical surveys and pharmacological screens. Based on these observations, X. caffra var. caffra was examined for its phytochemical composition and activity against the gonorrheal pathogen Neisseria gonorrhoeae. Initially, the leaf ethanolic extract was seen to be ac- tive (43.9% inhibition). The DCM partition of this extract (with 78.8% inhibition) was subjected to bioassay guided fractionation leading to the identification of the bisnorsesquiterpene vomifoliol which exhibited sig- nificant activity (63.1%) against N. gonorrhoeae.
- Published
- 2013
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29. The Population Dynamics and Ecological Effects of Garlic Mustard, Alliaria petiolata, in a Minnesota Oak Woodland
- Author
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Megan R. Whitney, Abby Colehour, Jo Daney, Jerald J. Dosch, Joseph O'Neil, Mark A. Davis, Margaret Pearson, Clare Macmillen, Elizabeth Foster, Emily Merrill, and Michael D. Anderson
- Subjects
education.field_of_study ,biology ,Ecology ,Population ,Introduced species ,Alliaria petiolata ,Woodland ,biology.organism_classification ,Belt transect ,Deciduous ,Forb ,education ,Ecology, Evolution, Behavior and Systematics ,Woody plant - Abstract
Garlic mustard, Alliaria petiolata (M. Bieb.) Cavara & Grande, is an introduced biennial forb that has commonly been referred to as highly invasive and as having substantial negative effects on other plants in the eastern deciduous forests of North America. However, several recent studies have documented only modest effects on other plant species, raising questions as to the extent of the threat really posed by A. petiolata. Alliaria petiolata often exhibits an alternating two-year life-history cycle, with high rosette years alternating with high flowering stem years. It has been proposed that this cycle is partly driven by intraspecific competition between the stems and the rosettes. In a two-year study, we extensively sampled A. petiolata in a Minnesota woodland at two spatial scales, including 6.5 km of belt transects in a 6.8 ha study grid (20 × 20 m cells) and 90 small sampling quadrats (1.0 × 0.5 m) within the grid. At the large scale, we compared seed bank abundance and diversity of other ...
- Published
- 2012
30. Apoptosis-inducing effects of distichamine and narciprimine, rare alkaloids of the plant family Amaryllidaceae
- Author
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Jaume Bastida, Jerald J. Nair, Lucie Rárová, Miroslav Strnad, and Johannes Van Staden
- Subjects
Cell Survival ,Stereochemistry ,Clinical Biochemistry ,Narciclasine ,Molecular Conformation ,Pharmaceutical Science ,Apoptosis ,Pancratistatin ,Biochemistry ,Cell Line ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Liliaceae ,Humans ,Structure–activity relationship ,Amaryllidaceae Alkaloids ,Cytotoxicity ,Molecular Biology ,Dose-Response Relationship, Drug ,biology ,Alkaloid ,Organic Chemistry ,Stereoisomerism ,Amaryllidaceae ,Phenanthrenes ,biology.organism_classification ,Lycorine ,Antineoplastic Agents, Phytogenic ,chemistry ,MCF-7 Cells ,Molecular Medicine ,Drug Screening Assays, Antitumor ,HeLa Cells - 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.
- Published
- 2012
31. ChemInform Abstract: New Alkaloids from Hippeastrum papilio (Ravenna) Van Scheepen
- Author
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José Angelo S. Zuanazzi, Luciana R. Tallini, Jerald J. Nair, Warley de Souza Borges, Ying Guo, Francesc Viladomat, Natalia B. Pigni, Laura Torras-Claveria, Jean Paulo de Andrade, and Jaume Bastida
- Subjects
biology ,Chemistry ,Hippeastrum papilio ,Botany ,General Medicine ,biology.organism_classification ,Ravenna - Published
- 2016
32. Cytotoxic Alkaloid Constituents of the Amaryllidaceae
- Author
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Johannes Van Staden, Jerald J. Nair, and Jaume Bastida
- Subjects
Traditional medicine ,biology ,Stereochemistry ,Alkaloid ,Narciclasine ,Amaryllidaceae ,Pancratistatin ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,Biological property ,Cytotoxic T cell ,heterocyclic compounds ,Isoquinoline ,Amaryllidaceae Alkaloids - Abstract
The Amaryllidaceae alkaloids are a group of isoquinoline alkaloids with a distinct array of structural diversity. These compounds have attracted widespread attention due to their manifold biological properties, of which their significance in motor neuron disease through the clinical representative galanthamine is most striking. The cytotoxic potential of Amaryllidaceae alkaloids has also been gaining ground following the advancement of its phenanthridones pancratistatin and narciclasine into clinical trials. This progress has sparked considerable interest in this plant family as a sustainable source of potential anticancer chemotherapeutics. Given this background, this review seeks to (1) examine the cytotoxic effects of Amaryllidaceae alkaloids in cancer cell lines, (2) provide a structural and pharmacophoric basis to these effects, and (3) highlight the various molecular mechanisms behind these activities.
- Published
- 2016
33. The brazilian Amaryllidaceae as a source of acetylcholinesterase inhibitory alkaloids
- Author
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Raquel Brandt Giordani, José Angelo S. Zuanazzi, Strahil Berkov, Francesc Viladomat, Natalia B. Pigni, Laura Torras-Claveria, Jaume Bastida, Jean Paulo de Andrade, Julie Henriette Antoinette Dutilh, Mercè Font-Bardia, Liana G. Sachett, Kelly Silveira da Silva Bueno, Teresa Calvet, Eduardo Luis Konrath, Amélia T. Henriques, Jerald J. Nair, and Warley de Souza Borges
- Subjects
SANGUININE ,Aché ,Plant Science ,Inhibitory postsynaptic potential ,01 natural sciences ,chemistry.chemical_compound ,Hippeastrum ,Alkaloids ,Ic50 values ,Alcaloides ,X-ray crystallography ,biology ,010405 organic chemistry ,Otras Ciencias Químicas ,Alkaloid ,Radiocristal·lografia ,Ciencias Químicas ,Amaryllidaceae ,biology.organism_classification ,Acetylcholinesterase ,language.human_language ,HIPPEASTRUM ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,Biochemistry ,Hippeastrum papilio ,language ,GALANTHAMINE ,GC-MS ,CIENCIAS NATURALES Y EXACTAS ,Biotechnology - Abstract
Nine Brazilian Amaryllidaceae species were studied for their alkaloid composition and acetylcholinesterase (AChE) inhibitory activity via GC?MS and a modified Ellman assay, respectively. A total of thirty-six alkaloids were identified in these plants, of which Hippeastrum papilio and H. glaucescens exhibited the highest galanthamine content and the best IC50 values against AChE. Furthermore, Hippeastrum vittatum and Rhodophiala bifida also showed notable AChE inhibitory effects. X-ray crystallographic data for four galanthamine-type compounds revealed significant differences in the orientation of the N-methyl group, which are shown to be related to AChE inhibition. Fil: de Andrade, Jean Paulo. Universidad de Barcelona; España. Universidade Federal do Rio Grande do Sul; Brasil. Universidad del Espiritu Santo; Brasil Fil: Giordani, Raquel B.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Torras-Claveria, Laura. Universidad de Barcelona; España. Universidad del Espiritu Santo; Brasil Fil: Pigni, Natalia Belen. Universidad de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; Argentina. Universidade Federal do Rio Grande do Sul; Brasil Fil: Berkov, Strahil. Universidad de Barcelona; España. AgroBioInstitute; Bulgaria. Universidad del Espiritu Santo; Brasil Fil: Font-Bardia, Mercè. Universidad de Barcelona; España Fil: Calvet, Teresa. Universidade Estadual de Campinas; Brasil Fil: Konrath, Eduardo Luis. Universidade Federal do Rio Grande do Sul; Brasil. Universidad del Espiritu Santo; Brasil Fil: Bueno, Kelly. Universidade Federal do Rio Grande do Sul; Brasil Fil: Sachett, Liana G.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Dutilh, Julie H.. Universidade Estadual de Campinas; Brasil. Universidad del Espiritu Santo; Brasil Fil: de Souza Borges, Warley. Universidad del Espiritu Santo; Brasil Fil: Viladomat, Francesc. Universidad de Barcelona; España Fil: Henriques, Amelia T.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Nair, Jerald J.. Universidad de Barcelona; España Fil: Zuanazzi, José Angelo S.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Bastida, Jaume. Universidad de Barcelona; España
- Published
- 2016
34. Isolation and quantification of the toxic methylazoxymethanol glycoside macrozamin in selected South African cycad species
- Author
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Johannes Van Staden and Jerald J. Nair
- Subjects
Macrozamin ,biology ,Plant Science ,biology.organism_classification ,Cycad ,chemistry.chemical_compound ,Habitat destruction ,Encephalartos transvenosus ,chemistry ,Botany ,Threatened species ,Cycasin ,IUCN Red List ,Conservation status ,Endemism ,Methylazoxymethanol - 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.
- Published
- 2012
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35. Antibacterial activity of crinane alkaloids from Boophone disticha (Amaryllidaceae)
- Author
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Johannes Van Staden, Jerald J. Nair, and L. Cheesman
- Subjects
Staphylococcus aureus ,Klebsiella pneumoniae ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,medicine.disease_cause ,Klebsiella ,Gram-Negative Bacteria ,Drug Discovery ,Botany ,Escherichia coli ,Liliaceae ,medicine ,Medicine, African Traditional ,Buphanidrine ,Pharmacology ,biology ,Traditional medicine ,Plant Extracts ,Boophone disticha ,Amaryllidaceae ,biology.organism_classification ,Anti-Bacterial Agents ,Phytochemical ,Amaryllidaceae Alkaloids ,Antibacterial activity ,Bacteria ,Bacillus subtilis - 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 0.063 mg/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 0.063 mg/ml. Their close structural similarity may have bearing on their similar activity profiles.
- Published
- 2012
36. Isolation of narciprimine from Cyrtanthus contractus (Amaryllidaceae) and evaluation of its acetylcholinesterase inhibitory activity
- Author
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Jerald J. Nair, Johannes Van Staden, and Adeyemi O. Aremu
- Subjects
Magnetic Resonance Spectroscopy ,Stereochemistry ,Plant Roots ,Mass Spectrometry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Liliaceae ,Animals ,Zephyranthes ,Pharmacology ,Chromatography ,Eels ,Plants, Medicinal ,Molecular Structure ,biology ,Traditional medicine ,Plant Extracts ,Amaryllidaceae ,Phenanthrenes ,biology.organism_classification ,Lycorine ,Acetylcholinesterase ,Narcissus ,Cyrtanthus ,chemistry ,Lycoris ,Amaryllidaceae Alkaloids ,Cholinesterase Inhibitors ,Pharmacophore - 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 (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.
- Published
- 2011
37. Structure–activity studies on acetylcholinesterase inhibition in the lycorine series of Amaryllidaceae alkaloids
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James McNulty, Jessamyn R. L. Little, John D. Brennan, Jerald J. Nair, and Jaume Bastida
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biology ,Stereochemistry ,Alkaloid ,Organic Chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Lycorine ,Biochemistry ,Chemical synthesis ,Acetylcholinesterase ,Structure-Activity Relationship ,chemistry.chemical_compound ,Alkaloids ,chemistry ,Enzyme inhibitor ,Drug Discovery ,biology.protein ,Molecular Medicine ,Structure–activity relationship ,Cholinesterase Inhibitors ,Pharmacophore ,Amaryllidaceae Alkaloids ,Molecular Biology - 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.
- Published
- 2010
38. Antifungal Activity Based Studies of Amaryllidaceae Plant Extracts
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Jerald J. Nair and Johannes Van Staden
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Pharmacology ,Antifungal ,medicine.medical_specialty ,biology ,010405 organic chemistry ,medicine.drug_class ,business.industry ,Plant Science ,General Medicine ,Amaryllidaceae ,Surgical procedures ,biology.organism_classification ,01 natural sciences ,Organ transplantation ,0104 chemical sciences ,Multiple drug resistance ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Infectious disease (medical specialty) ,Drug Discovery ,medicine ,business - Abstract
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
- Published
- 2017
39. Selective cytochrome P450 3A4 inhibitory activity of Amaryllidaceae alkaloids
- Author
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James McNulty, Denis J. Crankshaw, Alison C. Holloway, Mohini Singh, Jaume Bastida, and Jerald J. Nair
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Stereochemistry ,Clinical Biochemistry ,Narciclasine ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Pancratistatin ,Biochemistry ,Chemical synthesis ,Small Molecule Libraries ,chemistry.chemical_compound ,Drug Discovery ,Cytochrome P-450 CYP3A ,Humans ,Enzyme Inhibitors ,Amaryllidaceae Alkaloids ,Molecular Biology ,biology ,Galantamine ,Chemistry ,Alkaloid ,Organic Chemistry ,Cytochrome P450 ,Biological activity ,Isoquinolines ,Lycorine ,Phenanthridines ,biology.protein ,Cytochrome P-450 CYP3A Inhibitors ,Molecular Medicine - 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.
- Published
- 2009
40. Structure-activity studies on the lycorine pharmacophore: A potent inducer of apoptosis in human leukemia cells
- Author
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Jaume Bastida, James McNulty, Carly Griffin, Jerald J. Nair, and Siyaram Pandey
- Subjects
Narcissus bujei ,Programmed cell death ,Stereochemistry ,Chemical structure ,Apoptosis ,Plant Science ,Horticulture ,Biology ,01 natural sciences ,Biochemistry ,Jurkat cells ,Lycorine ,Article ,chemistry.chemical_compound ,Jurkat Cells ,Structure-Activity Relationship ,Alkaloid ,Humans ,Cytotoxicity ,Molecular Biology ,Molecular Structure ,010405 organic chemistry ,Amaryllidaceae ,Apoptosis-induction ,General Medicine ,Antineoplastic Agents, Phytogenic ,0104 chemical sciences ,Phenanthridines ,010404 medicinal & biomolecular chemistry ,chemistry ,Anticancer agent ,Amaryllidaceae Alkaloids ,Pharmacophore ,Drug Screening Assays, Antitumor - Abstract
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.
- Published
- 2009
41. Seed rain during initial colonization of abandoned pastures in the premontane wet forest zone of southern Costa Rica
- Author
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Chris J. Peterson, Jerald J. Dosch, and Bruce L. Haines
- Subjects
Wet season ,geography ,geography.geographical_feature_category ,Ecology ,Seed dispersal ,Species diversity ,Ecological succession ,Biology ,Pasture ,Agronomy ,Propagule ,Species richness ,Ecology, Evolution, Behavior and Systematics ,Woody plant - Abstract
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.
- Published
- 2007
42. Apoptosis-Inducing Effects of Amaryllidaceae Alkaloids
- Author
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Johannes Van Staden, Jerald J. Nair, and Jaume Bastida
- Subjects
Drug ,media_common.quotation_subject ,Molecular Conformation ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,Pancratistatin ,Biology ,Biochemistry ,chemistry.chemical_compound ,Neoplasms ,Drug Discovery ,Animals ,Humans ,Amaryllidaceae Alkaloids ,Mode of action ,media_common ,Alkaloid ,Organic Chemistry ,Amaryllidaceae ,biology.organism_classification ,Lycorine ,chemistry ,Cancer cell ,Molecular Medicine - Abstract
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.
- Published
- 2015
43. Alkaloids from
- Author
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Reto Brun, Carles Codina, Francesc Viladomat, William E. Campbell, Jerald J. Nair, and Jaume Bastida
- Subjects
Circular dichroism ,Nerine ,biology ,Stereochemistry ,Chemistry ,Alkaloid ,Biological activity ,Plant Science ,General Medicine ,Amaryllidaceae ,Horticulture ,biology.organism_classification ,Biochemistry ,Bulb ,chemistry.chemical_compound ,Organic chemistry ,Phenols ,Molecular Biology ,Two-dimensional nuclear magnetic resonance spectroscopy - 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.
- Published
- 2005
44. X-ray crystallographic structure determination of the smoke-derived karrikin KAR3
- Author
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Martin Pošta, H.B. Papenfus, Jerald J. Nair, J. Van Staden, Orde Q. Munro, and Petr Beier
- Subjects
Smoke ,Karrikin ,Germination ,Computational biology ,Plant growth regulator ,Plant Science ,Biology ,X-ray ,Chemical constituents ,Botany ,Molecular mechanism ,Economic potential - Abstract
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.
- Published
- 2013
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45. Distichamine, a chemotaxonomic marker for the genus Boophone Herb. (Amaryllidaceae)
- Author
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John C. Manning, J. Van Staden, and Jerald J. Nair
- Subjects
food.ingredient ,Distichamine ,biology ,Amaryllidaceae ,Boophone haemanthoides ,Plant Science ,Pancratistatin ,biology.organism_classification ,Lycorine ,Boophone ,Chemotaxonomy ,chemistry.chemical_compound ,food ,chemistry ,Herb ,Botany ,Taxonomy (biology) - Abstract
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.
- Published
- 2012
46. Transient appearance of amyloid precursor protein plaques in the brain of thymectomized rats after human leptomeningeal cell grafts
- Author
-
Jerald J. Bernstein, Lorraine A. DeGiorgio, and Laura Manuelidis
- Subjects
Male ,Apolipoprotein E ,Pathology ,medicine.medical_specialty ,Amyloid ,Amyloid beta ,Plaque, Amyloid ,Cathepsin D ,Diffusion ,Rats, Sprague-Dawley ,Amyloid beta-Protein Precursor ,Apolipoproteins E ,Meninges ,Alzheimer Disease ,mental disorders ,medicine ,Amyloid precursor protein ,Animals ,Humans ,Brain Tissue Transplantation ,Senile plaques ,Amyloid beta-Peptides ,Microglia ,biology ,Ubiquitin ,General Neuroscience ,Graft Survival ,P3 peptide ,Brain ,Thymectomy ,Rats ,Biochemistry of Alzheimer's disease ,Disease Models, Animal ,medicine.anatomical_structure ,biology.protein ,Lysosomes - Abstract
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.
- Published
- 2002
47. Alkaloid Constituents of the Amaryllidaceae Plant Amaryllis belladonna L
- Author
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Jean Paulo de Andrade, Luciana R. Tallini, Marcel Kaiser, Jaume Bastida, Jose Angelo Silveira Zuanazzi, Francesc Viladomat, Jerald J. Nair, and Universitat de Barcelona
- Subjects
Belladona (Drug) ,Amaryllis belladonna ,medicine.drug_class ,Trypanosoma cruzi ,Plasmodium falciparum ,Antiprotozoal Agents ,Leishmania donovani ,Belladona (Medicament) ,Pharmaceutical Science ,alkaloids ,01 natural sciences ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,Alkaloids ,lcsh:Organic chemistry ,Parasitic Sensitivity Tests ,parasitic diseases ,Drug Discovery ,Botany ,Alcaloides ,medicine ,Physical and Theoretical Chemistry ,Amaryllidaceae Alkaloids ,Amaryllidaceae ,biosynthetic pathways ,NMR ,MS ,biology ,Plant Extracts ,010405 organic chemistry ,Alkaloid ,Organic Chemistry ,biology.organism_classification ,Biosynthetic Pathways ,0104 chemical sciences ,Bulb ,Biosynthetic pathways ,010404 medicinal & biomolecular chemistry ,Chemistry (miscellaneous) ,Antiprotozoal ,Molecular Medicine - Abstract
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.
- Published
- 2017
48. Distribution and Diversity of Usage of the Amaryllidaceae in the Traditional Remediation of Infectious Diseases
- Author
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Anke Wilhelm, Johannes Van Staden, Jerald J. Nair, and Susanna L. Bonnet
- Subjects
Pharmacology ,010405 organic chemistry ,business.industry ,Plant Science ,General Medicine ,Disease ,Biology ,01 natural sciences ,0104 chemical sciences ,Biotechnology ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Infectious disease (medical specialty) ,Chemical constituents ,Drug Discovery ,Traditional knowledge ,business - Abstract
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.
- Published
- 2017
49. ChemInform Abstract: Alkaloids of the South African Amaryllidaceae: A Review
- Author
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Jerald J. Nair, Francesc Viladomat, Carles Codina, Jaume Bastida, and Johannes Van Staden
- Subjects
Traditional medicine ,biology ,Chemistry ,General Medicine ,Amaryllidaceae ,biology.organism_classification - Published
- 2014
50. Crinine-type alkaloids from Hippeastrum aulicum and H. calyptratum
- Author
-
Jaume Bastida, Jean Paulo de Andrade, Carles Codina, Jullie Dutilh, Jerald J. Nair, Ying Guo, Mercè Font-Bardia, Teresa Calvet, Francesc Viladomat, and Jose Angelo Silveira Zuanazzi
- Subjects
Circular dichroism ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Plant Science ,Horticulture ,Crystallography, X-Ray ,Biochemistry ,Hippeastrum ,Alkaloids ,Liliaceae ,Alcaloides ,Hippeastrum calyptratum ,Amaryllidaceae Alkaloids ,Molecular Biology ,X-ray crystallography ,Hippeastrum aulicum ,biology ,Molecular Structure ,Plant Extracts ,Alkaloid ,Radiocristal·lografia ,General Medicine ,Homolycorine ,Amaryllidaceae ,biology.organism_classification - Abstract
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.
- Published
- 2014
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