Nicholas Oberlies

**Expertise: Medicinal Chemistry and Pharmacognosy **Education: B.S., Miami University, 1992--Ph.D., Purdue, 1997.

There are 136 included publications by Nicholas Oberlies :

TitleDateViewsBrief Description
a-Pyrone Derivatives, Tetra/Hexahydroxanthones, and Cyclodepsipeptides from Two Freshwater Fungi 2017 88 Eighteen (1–18) and seven (1, 4, 6–8, 17 and 18) compounds were isolated from organic extracts of axenic cultures of two freshwater fungi Clohesyomyces sp. and Clohesyomyces aquaticus (Dothideomycetes, Ascomycota), respectively. Compounds 1–12 belong...
Acetophenone Derivatives from a Freshwater Fungal Isolate of Recently Described Lindgomyces Madisonensis (G416) 2016 73 The exploration of freshwater ascomycetes, which have undergone only limited investigation, may provide opportunities both to characterize new genera/species of fungi and to uncover new chemical diversity. In this study, seven acetophenone derivative...
Additions to Lindgomyces (Lindgomycetaceae, Pleosporales, Dothideomycetes), Including Two New Species Occurring on Submerged Wood from North Carolina, USA, with Notes on Secondary Metabolite Profiles 2017 91 Two new species of freshwater ascomycetes belonging to the genus Lindgomyces (Pleosporales, Dothideomycetes) are described and illustrated from submerged wood in North Carolina, USA. Lindgomyces carolinensis is characterized by immersed to erumpent a...
Analysis of herbal teas made from the leaves of comfrey (Symphytum officinale): reduction of N-oxides results in order of magnitude increases in the measurable concentration of pyrrolizidine alkaloids. 2004 4731 Objectives: To determine the relative quantities of two hepatotoxic pyrrolizidine alkaloids, symphytine and echimidine, in teas prepared from comfrey leaves (Symphytum officinale), and to determine the potential contribution of the N- oxide forms of ...
Angiopreventive Efficacy of Pure Flavonolignans from Milk Thistle Extract against Prostate Cancer: Targeting VEGF-VEGFR Signaling 2012 42 The role of neo-angiogenesis in prostate cancer (PCA) growth and metastasis is well established, but the development of effective and non-toxic pharmacological inhibitors of angiogenesis remains an unaccomplished goal. In this regard, targeting aberr...
The Annonaceous Acetogenin Bullatacin Is Cytotoxic against Multidrug Resistant Human Mammary Adenocarcinoma Cells 1997 77 Cytotoxic effects of the Annonaceous acetogenin, bullatacin, were studied in multidrug-resistant (MDR) human mammary adenocarcinoma (MCF-7/Adr) cells vs. the parental non-resistant wild type (MCF-7/wt) cells. Bullatacin was effectively cytotoxic to t...
Antimicrobial Fungal Endophytes from the Botanical Medicine Goldenseal (Hydrastis canadensis) 2016 54 The potential of fungal endophytes to alter or contribute to plant chemistry and biology has been the topic of a great deal of recent interest. For plants that are used medicinally, it has been proposed that endophytes might play an important role in...
Antimycobacterial Furofuran Lignans from the Roots of Anemopsis californica 2014 849 Topical preparations of Anemopsis californica have been used by Native American tribes in the southwestern United States and northern Mexico to treat inflammation and infections. We report results of bioassay-guided isolation conducted on a sample of...
Antioxidant activity and total phenolic content of aqueous and methanolic extracts of Jordanian plants: an ICBG project 2007 3721 As part of an International Cooperative Biodiversity Groups (ICBG) program to study Jordan's biodiversity, the relative levels of antioxidant activity and the total phenolic content of aqueous and methanolic extracts of a total of 95 plant species, a...
Benzoquinones and Terphenyl Compounds As Phosphodiesterase-4B Inhibitors from a Fungus of the Order Chaetothyriales (MSX 47445) 2013 669 Three bioactive compounds were isolated from an organic extract of an ascomycete fungus of the order Chaetothyriales (MSX 47445) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, two w...
Bioactive Withanolides from Withania obtusifolia 2014 67 Seven withanolides were isolated from the leaves of Withania obtusifolia. Of these, one was new [obtusifonolide (1)], five were new to the species [sitoindoside IX (2), 6a-chloro-5ß-hydroxy withaferin A (3), isowithanone (4), 2,3-dihydro-3-ethoxywith...
Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds 2016 50 [The original abstract for this article contains images that cannot be displayed here. Please click on the link below to read the full abstract and article.]
Biosynthesis of Fluorinated Peptaibols Using a Site-Directed Building Block Incorporation Approach 2017 69 Synthetic biological approaches, such as site-directed biosynthesis, have contributed to the expansion of the chemical space of natural products, making possible the biosynthesis of unnatural metabolites that otherwise would be difficult to access. S...
Biosynthetically Distinct Cytotoxic Polyketides from Setophoma terrestris 2015 44 Sixteen polyketides belonging to diverse structural classes, including monomeric/dimeric tetrahydroxanthones and resorcylic acid lactones, were isolated from an organic extract of a fungal culture Setophoma terrestris (MSX45109) by bioactivity-direct...
Characterization and Isolation of Peptide Metabolites of an Antifungal Bacterial Isolate Identified as Bacillus Amyloliquefaciens Subspecies plantarum Strain FZB42 2017 68 Some bacteria produce antimicrobial chemicals in their immediate environments. These antimicrobial agents are enzymes, polypeptides or non-protein organic compounds. In this study, a bacterial isolate that produces antifungal chemical(s) was isolated...
Chemoinformatic Expedition of the Chemical Space of Fungal Products 2016 39 Aim: Fungi are valuable resources for bioactive secondary metabolites. However, the chemical space of fungal secondary metabolites has been studied only on a limited basis. Herein, we report a comprehensive chemoinformatic analysis of a unique set of...
Chemoselective fluorination and chemoinformatic analysis of griseofulvin: Natural vs fluorinated fungal metabolites 2017 77 [2017-2018 UNCG University Libraries Open Access Publishing Fund Grant Winner.] Griseofulvin is a fungal metabolite and antifungal drug used for the treatment of dermatophytosis in both humans and animals. Recently, griseofulvin and its analogues hav...
Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions. 2007 3340 Most drugs are taken orally. For those intended to act systemically, a significant fraction of the dose can be eliminated during its first passage through a sequence of organs before entry into the general circulation. For some drugs, the degree of f...
Colchicinoids from Colchicum Crocifolium Boiss. (Colchicaceae) 2010 32 A new colchicinoid from Colchicum crocifolium Boiss. (Colchicaceae) was isolated and identified as N,N-dimethyl-N-deacetyl-(-)-cornigerine (5), along with four known compounds, but new to the species: (-)-colchicine (1), (-)-demecolcine (2), (-)-N-me...
Colchicinoids from Colchicum Crocifolium Boiss.: A Case Study in Dereplication Strategies for (-)-Colchicine and Related Analogs Using LC-MS and LC-PDA Techniques 2008 101 As a part of a project designed to investigate Colchicum species in Jordan, the chemical constituents of Colchicum crocifolium Boiss. (Colchicaceae) were investigated using LC-MS and LC–UV/Vis PDA. A decision tree for working with colchicinods has be...
Comparative SAR Evaluations of Annonaceous Acetogenins for Pesticidal Activity 1997 73 The activities of 44 Annonaceous acetogenins, which were originally isolated by monitoring plant fractionations with the brine shrimp lethality test (BST), were evaluated in the yellow fever mosquito larvae microtiter plate (YFM) assay. The results c...
Comparison of the chemistry and diversity of endophytes isolated from wild-harvested and greenhouse-cultivated yerba mansa (Anemopsis californica) 2015 440 With this study, we explored the identity and chemistry of fungal endophytes from the roots of yerba mansa [Anemopsis californica (Nutt.) Hook. & Arn. (Saururaceae)], a botanical traditionally used to treat infection. We compared the diversity of fun...
Comparison of Metabolomics Approaches for Evaluating the Variability of Complex Botanical Preparations: Green Tea (Camellia sinensis) as a Case Study 2017 66 A challenge that must be addressed when conducting studies with complex natural products is how to evaluate their complexity and variability. Traditional methods of quantifying a single or a small range of metabolites may not capture the full chemica...
Contrasting Roles of H3K4me3 and H3K9me3 in Regulation of Apoptosis and Gemcitabine Resistance in Human Pancreatic Cancer Cells 2018 30 Background: Pancreas ductal adenocarcinoma (PDAC) has the most dismal prognosis among all human cancers since it is highly resistant to chemotherapy, radiotherapy and immunotherapy. The anticipated consequence of all therapies is induction of tumor a...
Cyclodepsipeptides, Sesquiterpenoids, and Other Cytotoxic Metabolites from the Filamentous Fungus Trichothecium sp. (MSX 51320) 2011 727 Two new cyclodepsipeptides (1 and 2), two new sesquiterpenoids (3 and 4), and the known compounds guangomide A (5), roseotoxin S, and three simple trichothecenes were isolated from the cytotoxic organic extract of a terrestrial filamentous fungus, Tr...
Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae 2012 963 Bioactivity-directed fractionation of the organic extracts of two filamentous fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the Mycosynthetix library, led to the isolation of a new dimeric epipolythiodioxopiperazine alkaloid, vert...
Cytotoxic Xanthone-Anthraquinone Heterodimers from an Unidentified Fungus of the Order Hypocreales (MSX 17022) 2011 857 Two new xanthone-anthraquinone heterodimers, acremoxanthone C (5) and acremoxanthone D (2), have been isolated from an extract of an unidentified fungus of the Order Hypocreales (MSX 17022) by bioactivity-directed fractionation as part of a search fo...
Dendrimer-encapsulated camptothecins: Increased solubility, cellular uptake, and cellular retention affords enhanced anticancer activity in vitro. 2006 2149 A biocompatible polyester dendrimer composed of the natural metabolites, glycerol and succinic acid, is described for the encapsulation of the antitumor camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The cytotoxicity of the d...
Dereplicating and Spatial Mapping of Secondary Metabolites from Fungal Cultures in Situ 2015 576 Ambient ionization mass spectrometry techniques have recently become prevalent in natural product research due to their ability to examine secondary metabolites in situ. These techniques retain invaluable spatial and temporal details that are lost th...
Dereplication of Macrocyclic Trichothecenes from Extracts of Filamentous Fungi through UV and NMR Profiles 2010 1390 Macrocyclic trichothecenes, which have potent cytotoxicity, have been isolated from many different fungal species. These compounds were evaluated clinically by the U.S. National Cancer Institute in the 1970's and 1980's. However, they have yet to be ...
Detection of Adulteration in Hydrastis canadensis (Goldenseal) Dietary Supplements via Untargeted Mass Spectrometry-Based Metabolomics 2018 63 Current estimates report that approximately 25% of U.S. adults use dietary supplements for medicinal purposes. Yet, regulation and transparency within the dietary supplement industry remains a challenge, and economic incentives encourage adulteration...
Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma associated herpesvirus. 2007 1312 Tumors associated with Kaposi's sarcoma–associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent ...
Differential In Vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation 2011 1806 Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin is a major component of silymarin, consisting of the flavonolignans silybin A and sil...
Discovery of anticancer agents of diverse natural origin 2009 5252 A collaborative multidisciplinary research project is described in which new natural product anticancer drug leads are obtained from a diverse group of organisms, constituted by tropical plants, aquatic cyanobacteria, and filamentous fungi. Informati...
Discovery of Anticancer Agents of Diverse Natural Origin 2016 49 Recent progress is described in an ongoing collaborative multidisciplinary research project directed towards the purification, structural characterization, chemical modification, and biological evaluation of new potential natural product anticancer a...
Diterpene glycosides from Egletes Viscosa 2005 1515 A phytochemical investigation of the CHCl3-soluble extract of the entire plant of Egletes viscosa (Asteraceae), collected in Peru, afforded two new labdane glycosides, 13-hydroxy-7-oxolabda8,14-diene 13(R)-0-a-L-arabinopyranoside and 13–hydroxy-7-oxo...
DNA Barcoding for Identification of Consumer-Relevant Mushrooms: A Partial Solution for Product Certification? 2017 71 One challenge in the dietary supplement industry is confirmation of species identity for processed raw materials, i.e. those modified by milling, drying, or extraction, which move through a multilevel supply chain before reaching the finished product...
Effects of (5z)-7-Oxozeaenol on MDA-MB-231 Breast Cancer Cells 2012 43 Aim: (5Z)-7-Oxozeaenol was studied to reveal the path through which it exerts its effects on triple-negative MDA-MB-231 breast cancer cells. Materials and Methods: The apoptotic effect of (5Z)-7-oxozeaenol on MDA-MB-231 cancer cells was analyzed by c...
Effects of (5z)-7-Oxozeaenol on the Oxidative Pathway of Cancer Cells 2012 85 Aim: As part of an on going investigation of novel anticancer agents from natural origin, the biological and cellular effects of (5Z)-7-oxozeaenol on cancer cells were investigated. Materials and Methods: The expression of nuclear factor kappa B (NF-...
Enhanced Bioactivity of silybin B methylation Products 2013 697 Flavonolignans from milk thistle (Silybum marianum) have been investigated for their cellular modulatory properties, including cancer chemoprevention and hepatoprotection, as an extract (silymarin), as partially purified mixtures (silibinin and isosi...
Enhanced Dereplication of Fungal Cultures Via Use of Mass Defect Filtering 2017 52 Effective and rapid dereplication is a hallmark of present-day drug discovery from natural sources. This project strove to both decrease the time and expand the structural diversity associated with dereplication methodologies. A 5?min liquid chromato...
Epigenetic Manipulation of a Filamentous Fungus by the Proteasome-Inhibitor Bortezomib Induces the Production of an Additional Secondary Metabolite 2014 54 The use of epigenetic modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, has been explored increasingly as a technique to induce the production of additional microbial secondary metabolites. The application of suc...
Ethanolic Echinacea purpurea Extracts Contain a Mixture of Cytokine-Suppressive and Cytokine-Inducing Compounds, Including Some That Originate from Endophytic Bacteria 2015 1352 Echinacea preparations, which are used for the prevention and treatment of upper respiratory infections, account for 10% of the dietary supplement market in the U.S., with sales totaling more than $100 million annually. In an attempt to shed light on...
Evaluation of culture media for the production of secondary metabolites in a natural products screening program 2013 1092 Variation in the growing environment can have significant impacts on the quantity and diversity of fungal secondary metabolites. In the industrial setting, optimization of growing conditions can lead to significantly increased production of a compoun...
Flavonolignans from Aspergillus iizukae, a Fungal Endophyte of Milk Thistle (Silybum marianum) 2014 808 Silybin A (1), silybin B (2), and isosilybin A (3), three of the seven flavonolignans that constitute silymarin, an extract of the fruits of milk thistle (Silybum marianum), were detected for the first time from a fungal endophyte, Aspergillus iizuka...
Freshwater Ascomycetes: Minutisphaera (Dothideomycetes) revisited, including one new species from Japan 2013 969 During investigations of freshwater ascomycetes we found one interesting taxon from Aomori (Japan), as well as three additional taxa from North Carolina (USA), which were morphologically similar to Minutisphaera, a recently described freshwater fungu...
Freshwater Ascomycetes: Minutisphaera (Dothideomycetes) revisited, including one new species from Japan 2013 1593 During investigations of freshwater ascomycetes we found one interesting taxon from Aomori (Japan), as well as three additional taxa from North Carolina (USA), which were morphologically similar to Minutisphaera, a recently described freshwater fung...
Fungal Identification Using Molecular Tools: A Primer for the Natural Products Research Community 2017 91 Fungi are morphologically, ecologically, metabolically, and phylogenetically diverse. They are known to produce numerous bioactive molecules, which makes them very useful for natural products researchers in their pursuit of discovering new chemical d...
Fungal Planet Description Sheets: 371-399 2015 73 Novel species of fungi described in the present study include the following from Australia:Neoseptorioides eucalypti gen. & sp. nov. from Eucalyptus radiata leaves, Phytophthoragondwanensis from soil, Diaporthe tulliensis from rotted stem ends of The...
Gram-scale purification of flavonolignan diastereoisomers from Silybum marianum (Milk Thistle) extract in support of preclinical in vivo studies for prostate cancer chemoprevention 2007 4211 Extracts of milk thistle (Silybum marianum, Asteraceae), termed "silymarin," are used worldwide, primarily for hepatoprotective applications and recently for prostate cancer chemoprevention. Silymarin is a mixture of at least eight compounds, and fou...
Graviola Inhibits Hypoxia-Induced NADPH Oxidase Activity in Prostate Cancer Cells Reducing Their Proliferation and Clonogenicity 2016 29 Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with...
Greensporone C, a Freshwater Fungal Secondary Metabolite Induces Mitochondrial-Mediated Apoptotic Cell Death in Leukemic Cell Lines 2018 49 Therapeutic agents used in the treatment of cancer are known to develop resistance against cancer cells. Hence, there is a continuing need to investigate novel agents for the treatment and management of cancer. Antitumor activity of greensporone C (G...
Greensporones: Resorcylic Acid Lactones from an Aquatic Halenospora sp. 2014 670 Fourteen new resorcylic acid lactones (1–14) were isolated from an organic extract of a culture of a freshwater aquatic fungus Halenospora sp. originating from a stream in North Carolina. The structures were elucidated using a set of spectroscopic an...
HiFSA Fingerprinting Applied to Isomers with Near-Identical NMR Spectra: The Silybin/Isosilybin Case 2013 947 This study demonstrates how regio- and diastereo-isomers with near-identical NMR spectra can be distinguished and unambiguously assigned using quantum mechanical driven 1H iterative Full Spin Analysis (HiFSA). The method is illustrated with four natu...
Identification of hepatoprotective flavonolignans from silymarin 2010 889 Silymarin, also known as milk thistle extract, inhibits hepatitis C virus (HCV) infection and also displays antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. In the current study, we evaluat...
Identification of Isosilybin a from Milk Thistle Seeds as an Agonist of Peroxisome Proliferator-Activated Receptor Gamma 2014 34 Peroxisome proliferator-activated receptor gamma (PPAR?) is a key regulator of glucose and lipid metabolism. Agonists of this nuclear receptor are used in the treatment of type 2 diabetes and are also studied as a potential treatment of other metabol...
Identifying the Differential Effects of Silymarin Constituents on Cell Growth and Cell Cycle Regulatory Molecules in Human Prostate Cancer Cells 2008 40 Prostate cancer (PCa) is the leading cause of cancer-related deaths in men; urgent measures are warranted to lower this deadly malignancy. Silymarin is a known cancer chemopreventive agent, but the relative anticancer efficacy of its constituents is ...
In Situ Analysis of Asimina triloba (Paw Paw) Plant Tissues for Acetogenins via the Droplet-Liquid Microjunction-Surface Sampling Probe Coupled to UHPLC-PDA-HRMS/MS 2016 63 Asimina triloba, commonly known as paw paw, is one of approximately 2100 species in the Annonaceae family, scores of which are known to biosynthesize bioactive secondary metabolites, termed Annonaceous acetogenins. Even with over 400 acetogenins iden...
Influence of Dietary Substances on Intestinal Drug Metabolism and Transport 2010 4398 Successful delivery of promising new chemical entities via the oral route is rife with challenges, some of which cannot be explained or foreseen during drug development. Further complicating an already multifaceted problem is the obvious, yet often o...
Isochromenones, isobenzofuranone, and tetrahydronaphthalenes produced by Paraphoma radicina, a fungus isolated from a freshwater habitat 2014 885 Six isochromenones (1–6), clearanols F (5) and G (6), one isobenzofuranone (7), and two tetrahydronaphthalene derivatives (8 and radinaphthalenone (9)), were isolated and identified from a culture of the fungus Paraphoma radicina, which was isolated ...
Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) using Human Intestinal Microsomes 2010 1984 Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential dru...
Isolation, Semisynthesis, Covalent Docking and Transforming Growth Factor Beta-Activated Kinase 1 (TAK1)-Inhibitory Activities of (5Z)-7-Oxozeaenol Analogues 2015 71 (5Z)-7-Oxozeanol and related analogues were isolated and screened to explore their activity as TAK1 inhibitors. Seven analogues were synthesized and more than a score of natural products isolated that examined the role that different areas of the mol...
Isosilibinin Inhibits Advanced Human Prostate Cancer Growth in Athymic Nude Mice: Comparison with Silymarin and Silibinin 2008 28 Earlier studies have shown the cancer chemopreventive efficacy of silymarin and its semi-purified constituent silibinin against prostate cancer (PCa), but the efficacy of other constituents of silymarin is largely unknown. In the present study, we as...
Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. 2007 1243 Silymarin and, one of its constituents, silibinin exert strong efficacy against prostate cancer (PCA); however, anticancer efficacy and associated mechanisms of other components of silymarin, which is a mixture of flavonolignans, are largely unknown....
Isosilybin B causes androgen receptor degradation in human prostate carcinoma cells via PI3K-Akt-Mdm2-mediated pathway 2008 1976 The identification and development of novel nontoxic phytochemicals that target androgen and androgen receptor (AR) signaling remains a priority for prostate cancer (PCA) control. In the present study, we assessed the antiandrogenic efficacy of isosi...
Isosilybin A Induces Apoptosis in Human Prostate Cancer Cells Via Targeting Akt, NF-kappaB, and Androgen Receptor Signaling 2010 38 Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in P...
Labeled Content of Two Furanocoumarins in Dietary Supplements Correlates with Neither Actual Content nor CYP3A Inhibitory Activity 2014 48 Dietary supplements are a multi-billion dollar business, with yearly profit increases. Allegedly safe, these supplements are marketed to a variety of niches, encompassing claims from immune support to weight loss. Six sports nutrition supplements wer...
Large-Scale Isolation of Flavonolignans from Silybum marianum Extract Affords New Minor Constituents and Preliminary Structure-Activity Relationships 2010 511 The gram-scale isolation of the major flavonolignan diastereoisomers from milk thistle (Silybum marianum) extract provided an entré into the isolation of two related analogs that are present in extremely minute quantities. The isolation and structure...
Lindgomyces angustiascus, (Lindgomycetaceae, Pleosporales, Dothideomycetes), a new lignicolous species from freshwater habitats in the USA 2013 789 In this paper, we describe and illustrate a new species, Lindgomyces angustiascus, from submerged wood in lotic and lentic habitats from Florida, North Carolina and Wisconsin, USA. The new species is characterized by black, partially immersed, flatte...
Lindgomyces angustiascus, (Lindgomycetaceae, Pleosporales, Dothideomycetes), a new lignicolous species from freshwater habitats in the USA 2013 841 In this paper, we describe and illustrate a new species, Lindgomyces angustiascus, from submerged wood in lotic and lentic habitats from Florida, North Carolina and Wisconsin, USA. The new species is characterized by black, partially immersed, flatte...
Mapping of sample collection data: GIS tools for the natural product researcher 2009 1397 Scientists engaged in the research of natural products often either conduct field collections themselves or collaborate with partners who do, such as botanists, mycologists, or SCUBA divers. The information gleaned from such collecting trips (e.g. lo...
Mass Spectrometry Imaging of Secondary Metabolites Directly on Fungal Cultures 2014 57 Desorption electrospray ionization mass spectrometry (DESI-MS) is an ambient ionization technique that enables imaging experiments directly on fungal cultures. Much information can be gained by examining an organism directly from culture, rather than...
Mechanisms Underlying Food–Drug Interactions: Inhibition of Intestinal Metabolism and Transport 2012 47 Food–drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic a...
Mechanistic Study of the Biomimetic Synthesis of Flavonolignan Diastereoisomers in Milk Thistle 2013 910 The mechanism for the biomimetic synthesis of flavonolignan diastereoisomers in milk thistle is proposed to proceed by single-electron oxidation of coniferyl alcohol, subsequent reaction with one of the oxygen atoms of taxifolin’s catechol moiety, an...
Meroterpenoids from Neosetophoma sp.: A Dioxa[4.3.3]propellane Ring System, Potent Cytotoxicity, and Prolific Expression 2019 78 Six fungal metabolites, of which five were new, including one (1) with a dioxa[4.3.3]propellane ring system, were discovered, identified, and structurally elucidated from Neosetophoma sp. (strain MSX50044); these compounds are similar to the bis-trop...
Microbial- mediated release of bisphenol A from polycarbonate vessels. 2008 1350 Aim: To identify the source of bisphenol A (BPA) [2,2'-bis(4-hydroxyphenyl) propane] in cultures of an antibiotic-producing Bacillus sp. strain grown in polycarbonate flasks. Methods and Results: Although a culture of an antibiotic-producing Bacillu...
Milk thistle and prostate cancer: Differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. 2005 1891 Extracts from the seeds of milk thistle, Silybum marianum, are known commonly as silibinin and silymarin and possess anticancer actions on human prostate carcinoma in vitro and in vivo. Seven distinct flavonolignan compounds and a flavonoid have been...
Milk thistle nomenclature: Why it matters in cancer research and pharmacokinetic studies. 2007 4008 Extracts of milk thistle have been recognized for centuries as "liver tonics" and are well-known to prevent or reverse hepatotoxicity of reactive drug metabolites or naturally occurring toxins. Milk thistle extracts are now under intense study in the...
Minutisphaerales (Dothideomycetes, Ascomycota): a new order of freshwater ascomycetes including a new family, Minutisphaeraceae, and two new species from North Carolina, USA 2015 984 Minutisphaera is a recently established genus of freshwater Dothideomycetes characterized by small, globose to subglobose or apothecioid, erumpent to superficial, brown ascomata; fissitunicate, eight-spored, ovoid to obclavate asci; and 1–2-septate, ...
The MLL1-H3K4me3 Axis-Mediated PD-L1 Expression and Pancreatic Cancer Immune Evasion 2017 48 Background: Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mech...
Mode of action of bullatacin, a potent antitumor acetogenin: Inhibition of NADH oxidase activity of HeLa and HL-60, but not liver, plasma membranes. 1995 4615 Bullatacin, a potential antitumor substance isolated from plants of the Annonaceae, and analogs of bullatacin, known collectively as acetogenins, have been reported previously to show potent activity in the inhibition of growth of murine tumors and h...
A Modified Grapefruit Juice Eliminates Two Compound Classes as Major Mediators of the Grapefruit Juice–Fexofenadine Interaction: An In Vitro–In Vivo “Connect” 2013 1009 The grapefruit juice (GFJ)–fexofenadine interaction involves inhibition of intestinal organic anion transporting polypeptide (OATP)-mediated uptake. Only naringin has been shown clinically to inhibit intestinal OATP; other constituents have not been ...
The most widely recognized mushroom: Chemistry of the genus Amanita. 2005 3940 Many review papers have been published on mushrooms of the genus Amanita, as these are well known to both scientific and lay audiences, probably due to the toxic and/or hallucinogenic properties of some species. This article aims to supplement the co...
Multiple Effects of Silymarin on the Hepatitis C Virus Lifecycle 2010 1591 Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's a...
Myosin Isoform Shifts and Decreased Reactivity in Hypoxia-Induced Hypertensive Pulmonary Arterial Muscle 1998 43 The principal stimulus that evokes pulmonary hypertension is chronic alveolar hypoxia. Pulmonary hypertension is associated with remodeling of the vessel walls, involving hypertrophy and hyperplasia of pulmonary arterial smooth muscle (PASM) and a co...
Nanoparticle Drug-Delivery Systems for Peritoneal Cancers: A Case Study of the Design, Characterization and Development of the Expansile Nanoparticle 2017 29 Nanoparticle (NP)-based drug-delivery systems are frequently employed to improve the intravenous administration of chemotherapy; however, few reports explore their application as an intraperitoneal therapy. We developed a pH-responsive expansile nano...
New Diketopiperazine Dimer from a Filamentous Fungal Isolate of Aspergillus sydowii 2015 32 Prior investigations of filamentous fungi in our group have resulted in the isolation of several new and biologically active natural products.[1-3] Continuing these investigations, we have now analyzed the metabolites from a fungal isolate of Aspergi...
A novel small molecule that selectively inhibits glioblastoma cells expressing EGFRvIII. 2007 1271 Background: Mutations of the epidermal growth factor receptor (EGFR) are a possible molecular target for cancer therapy. EGFR is frequently amplified in glioblastomas and 30 to 40% of glioblastomas also express the deletion mutation EGFRvIII. This fr...
Novel Strategies for the Discovery of Plant-Derived Anticancer Agents. 2003 8571 Work has continued on the investigation of plants, collected mainly from tropical rainforests, as potential sources of new cancer chemotherapeutic agents. About 400 primary samples are obtained each year, with the chloroform-soluble extract of each b...
Obionin B: an o-pyranonaphthoquinone decaketide from an unidentified fungus (MSX 63619) from the order Pleosporales 2011 530 A fungal extract (MSX 63619), from the Mycosynthetix library of over 50,000 fungi, displayed promising cytotoxicity against a human tumor cell panel. Bioactivity-directed fractionation led to the isolation of an o-pyranonaphthoquinone decaketide, whi...
Oleanolic Acid, a Bioactive Component of the Leaves of Ocimum Gratissimum (Lamiaceae) 1997 45 Bioactivity-guided fractionation of the leaves of Ocimum gratissimum L. (Lamiaceae), using the brine shrimp lethality test, led to the isolation of oleanolic acid. Oleanolic acid showed bioactivity against a panel of six human solid tumor cell lines,...
Optimizing Production and Evaluating Biosynthesis in Situ of a Herbicidal Compound, Mevalocidin, from Coniolariella Sp. 2016 65 Mevalocidin is a fungal secondary metabolite produced by Coniolariella sp. It is a unique phytotoxin that demonstrates broad spectrum post-emergent herbicidal properties. With limited options for weed control, the commercialization of a natural produ...
Pannorin B, a New Naphthopyrone from an Endophytic Fungal Isolate of Penicillium Sp. 2016 35 The herbal remedy, milk thistle (Silybum marianum), has been used in traditional medicine for various liver, kidney, and gall bladder ailments. For over a decade, our research group has been investigating the flavonolignans obtained from this medicin...
Peptaibols from Two Unidentified Fungi of the Order Hypocreales with Cytotoxic, Antibiotic, and Anthelmintic Activities 2012 67 As part of an ongoing investigation of filamentous fungi for anticancer leads, an active culture was identified from the Mycosynthetix library (MSX 70741, of the order Hypocreales, Ascomycota). The fungal extract exhibited cytotoxic activity against ...
Peptaibols, Tetramic Acid Derivatives, Isocoumarins, and Sesquiterpenes from a Bionectria sp. (MSX 47401) 2013 587 An extract of the filamentous fungus Bionectria sp. (MSX 47401) showed both promising cytotoxic activity (>90% inhibition of H460 cell growth at 20 µg/mL) and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). A bioact...
Phylogenetic and chemical diversity of fungal endophytes isolated from Silybum marianum (L) Gaertn. (milk thistle) 2015 697 Use of the herb milk thistle (Silybum marianum) is widespread, and its chemistry has been studied for over 50 years. However, milk thistle endophytes have not been studied previously for their fungal and chemical diversity. We examined the fungal end...
Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction 2014 1146 Herb–drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb–drug interactions using the semipurified milk thistle preparation, silibinin, as an ...
Phytochemical studies and cytotoxicity evaluations of Colchicum tunicatum Feinbr and Colchicum hierosolymitanum Feinbr (Colchicaceae): Two native Jordanian meadow saffrons. 2006 2529 As a part of our continuing investigation of Jordanian Colchicum species, the biologically active components of Colchicum hierosolymitanum Feinbr and Colchicum tunicatum Feinbr (Colchicaceae) were pursued. The brine shrimp lethality test (BSLT) was u...
Plasma Pharmacokinetics and Bioavailability of Verticillin A Following Different Routes of Administration in Mice Using Liquid Chromatography Tandem Mass Spectrometry 2017 2 Verticillin A is a natural product isolated from fungal cultures and has displayed potent antibiotic, antiviral, nematocidal, and anticancer properties in vitro. While in vivo studies have been limited due to sparse supply, the in vivo efficacy data ...
Polyhydroxyanthraquinones as Quorum Sensing Inhibitors from the Guttates of Penicillium restrictum and Their Analysis by Desorption Electrospray Ionization Mass Spectrometry 2014 884 The endophytic fungus Penicillium restrictum was isolated from the stems of a milk thistle (Silybum marianum) plant. In culture, the fungus produced distinct red guttates, which have been virtually uninvestigated, particularly from the standpoint of ...
Prealamethicin F50 and Related Peptaibols from Trichoderma arundinaceum: Validation of their Authenticity via in situ Chemical Analysis 2017 69 In the field of natural products chemistry, a common question pertains to the authenticity of an isolated compound, i.e. are the interesting side chains biosynthesized naturally or an artefact of the isolation/purification processes? The droplet-liqu...
Proliferation of antibiotic-producing bacteria and concomitant antibiotic production as the basis for the antibiotic activity of Jordan’s Red Soils. 2009 1668 Anecdotes, both historical and recent, recount the curing of skin infections, including diaper rash, by using red soils from the Hashemite Kingdom of Jordan. Following inoculation of red soils isolated from geographically separate areas of Jordan, Mi...
Pyrrolizidine alkaloids from Echium glomeratum (Boraginaceae). 2008 2223 The methanolic extract of the whole plant of Echium glomeratum Poir. (Boraginaceae) has afforded five pyrrolizidine alkaloids, three that were (7S, 8R)-petranine (1), (7S, 8S)-petranine (2), and (7R, 8R)-petranine (3a) or (7R, 8S)-petranine (3b), com...
qNMR for Profiling the Production of Fungal Secondary Metabolites 2017 77 Analysis of complex mixtures is a common challenge in natural products research. Quantitative nuclear magnetic resonance spectroscopy offers analysis of complex mixtures at early stages and with benefits that are orthogonal to more common methods of ...
A Randomized, Controlled, Double-Blind, Pilot Study of Milk Thistle for the Treatment of Hepatotoxicity in Childhood Acute Lymphoblastic Leukemia (ALL) 2010 29 BACKGROUND: Despite limited preclinical and clinical investigations, milk thistle (MT) is often used for the treatment of chemotherapy-associated hepatotoxicity. Limited treatment options exist for chemotherapy-related hepatoxicity. Given the wide us...
Rapid Quantitation of Furanocoumarins and Flavonoids in Grapefruit Juice using Ultra-Performance Liquid Chromatography 2013 1517 Introduction:Grapefruit juice can increase or decrease the systemic exposure of myriad oral medications, leading to untoward effects or reduced efficacy. Furanocoumarins in grapefruit juice have been established as inhibitors of cytochrome P450 3A (C...
Recent advances in Annonaceous acetogenins. 1996 12498 Annonaceous acetogenins are waxy substances consisting of C32 or C34 long chain fatty acids which have been combined with a propan-2-ol unit at C-2 to form a gama-lactone. They are only found in several genera of the plant family, Annonaceae. Their d...
Reinforcement of Polymeric Nanoassemblies for Ultra-High Drug Loadings, Modulation of Stiffness and Release Kinetics, and Sustained Therapeutic Efficacy 2018 2 The optimization of current polymeric nanoparticle therapies is restricted by low drug loadings and limited tunability of core properties. To overcome these shortcomings, a novel self-association approach is utilized to fabricate a dual-loaded poly(1...
Resorcylic Acid Lactones with Cytotoxic and NF-KB Inhibitory Activities and Their Structure–Activity Relationships 2011 726 As part of our ongoing investigation of filamentous fungi for anticancer leads, an active fungal extract was identified from the Mycosynthetix library (MSX 63935; related to Phoma sp.). The initial extract exhibited cytotoxic activity against the H46...
Revisiting the Enniatins: A Review of Their Isolation, Biosynthesis, Structure Determination and Biological Activities 2012 55 Enniatins are cyclohexadepsipeptides isolated largely from Fusariumspecies of fungi, although they have been isolated from other genera, such as Verticillium and Halosarpheia. They were first described over 60 years ago, and their range of biological...
Romidepsin (Istodax, NSC 630176, FR901228, FK228, Depsipeptide): A Natural Product Recently Approved for Cutaneous T-Cell Lymphoma 2011 73 Romidepsin (Istodax), a selective inhibitor of histone deacetylases (HDACs), was approved for the treatment of cutaneous T-cell lymphoma in November 2009 by the US Food and Drug Administration. This unique natural product was discovered from cultures...
Safety Assessment of Mushrooms in Dietary Supplements by Combining Analytical Data with in Silico Toxicology Evaluation 2017 87 Despite growing popularity in dietary supplements, many medicinal mushrooms have not been evaluated for their safe human consumption using modern techniques. The multifaceted approach described here relies on five key principles to evaluate the safet...
Sarothrin from Alkanna orientalis Is an Antimicrobial Agent and Efflux Pump Inhibitor 2013 1045 An Alkanna orientalis leaf and flower extract inhibited the growth of Staphylococcus aureus, a pathogen that causes an estimated 478000 hospitalizations in the US annually. Bioassay-guided fractionation of A. orientalis resulted in isolation of the f...
Scaffold Diversity of Fungal Metabolites 2017 37 Many drug discovery projects rely on commercial compounds to discover active leads. However, current commercial libraries, with mostly synthetic compounds, access a small fraction of the possible chemical diversity. Natural products, in contrast, pos...
Secondary Metabolites from Fungal Endophytes of Echinacea purpurea Suppress Cytokine Secretion by Macrophage-Type Cells 2016 48 Botanical extracts of Echinacea purpurea have been widely used for the treatment of upper respiratory infections. We sought to chemically examine fungal endophytes inhabiting E. purpurea, and to identify compounds produced by these endophytes with in...
Semisynthesis, Cytotoxicity, Antiviral Activity, and Drug Interaction Liability of 7-O-methylated Analogues of Flavonolignans from Milk Thistle 2013 1307 Silymarin, an extract of the seeds of milk thistle (Silybum marianum), is used as an herbal remedy, particularly for hepatoprotection. The main chemical constituents in silymarin are seven flavonolignans. Recent studies explored the non-selective met...
Silibinin inhibits hepatitis C virus entry into hepatocytes by hindering clathrin-dependent trafficking 2013 1441 Hepatitis C virus (HCV) is a global health concern infecting 170 million people worldwide. Previous studies indicate that the extract from milk thistle known as silymarin and its main component silibinin inhibit HCV infection. Here we investigated th...
Silymarin Constituents Enhance ABCA1 Expression in THP-1 Macrophages 2015 29 Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, i...
Silymarin for HCV infection 2013 1229 Silymarin, an extract of milk thistle seeds, and silymarin-derived compounds have been considered hepatoprotective since the plant was first described in ancient times. Hepatoprotection is defined as several non-mutually exclusive biological activiti...
Silymarin Inhibits in Vitro T Cell Proliferation and Cytokine Production in Hepatitis C Virus Infection 2010 38 Background and Aims: Silymarin, an extract from the seeds of the milk thistle plant Silybum marianum, has been used for centuries for the treatment of chronic liver diseases. Despite common use by patients with hepatitis C in the U.S., its clinical e...
Simple and inexpensive methods to prevent botanical misfortune. 2006 1989 Botanical dietary supplements are often targeted by the mainstream media and scientific/medical communities as being unscientific and unsafe relative to prescription pharmaceuticals and over-the counter drugs. However, the relative risk of botanical ...
Sorbicillinoid Analogs with Cytotoxic and Selective Anti-Aspergillus Activities from Scytalidium album 2014 67 As part of an ongoing project to explore filamentous fungi for anticancer and antibiotic leads, 11 compounds were isolated and identified from an organic extract of the fungus Scytalidium album (MSX51631) using bioactivity-directed fractionation agai...
Spatial and Temporal Profiling of Griseofulvin Production in Xylaria cubensis Using Mass Spectrometry Mapping 2016 63 A large portion of natural products research revolves around the discovery of new, bioactive chemical entities; however, studies to probe the biological purpose of such secondary metabolites for the host organism are often limited. Mass spectrometry ...
Spiroscytalin, a New Tetramic Acid and Other Metabolites of Mixed Biogenesis from Scytalidium cuboideum 2015 58 Spiroscytalin (1), a new tetramic acid that possesses an uncommon spiro-ring fusion between a polyketide-derived octalin ring system and a 2,4-pyrrolidinedione, along with two known compounds, leporin B (2) and purpactin A (3), were isolated from a s...
Synergistic antimicrobial activity of metabolites produced by a nonobligate bacterial predator 2003 1321 A naturally occurring, gram-negative, nonobligate predator bacterial strain 679-2, exhibits broad-spectrum antimicrobial activity that is due, in part, to the production of three extracellular compounds. Antimicrobial-activity-directed fractionation ...
Synergy-Directed Fractionation of Botanical Medicines: A Case Study with Goldenseal (Hydrastis canadensis) 2011 777 It is often argued that the efficacy of herbal medicines is a result of the combined action of multiple constituents that work synergistically or additively. Determining the bioactive constituents in these mixtures poses a significant challenge. We h...
Synthesis of Poly(1,2-Glycerol Carbonate)-Paclitaxel Conjugates and Their Utility as a Single High-Dose Replacement for Multi-Dose Treatment Regimens in Peritoneal Cancer 2017 34 Current chemotherapeutic dosing strategies are limited by the toxicity of anticancer agents and therefore rely on multiple low-dose administrations. As an alternative, we describe a novel sustained-release, biodegradable polymeric nanocarrier as a si...
Talarolutins A–D: Meroterpenoids from an Endophytic Fungal Isolate of Talaromyces minioluteus 2016 45 Four meroterpenoids [talarolutins A–D] and one known compound [purpurquinone A] were characterized from an endophytic fungal isolate of Talaromyces minioluteus (G413), which was obtained from the leaves of the medicinal plant milk thistle [Silybum ma...
Thielavin B Methyl Ester: A Cytotoxic Benzoate Trimer from an Unidentified Fungus (MSX 55526) from the Order Sordariales 2011 59 As part of our ongoing investigation of filamentous fungi for anticancer leads, an active fungal extract was identified from the Mycosynthetix library (MSX 55526; from the Order Sordariales). Bioactivity-directed fractionation yielded the known ergos...
Tumor Cell Growth Inhibition by Several Annonaceous Acetogenins in an in Vitro Disk Diffusion Assay 1995 65 The cell inhibition activities of several Annonaceous acetogenins, covering the three major structural classes of bis-adjacent, bis-non-adjacent, and single tetrahydrofuran (THF) ring compounds and their respective ketolactone rearrangement products,...
Use of the Hollow Fiber Assay for the Discovery of Novel Anticancer Agents from Fungi 2012 66 The hollow fiber assay (HFA) is a drug discovery tool to aid investigators in the prioritization of lead compounds identified by in vitro testing for further development in animal models of disease. In the HFA, cells are cultured in hollow fibers con...
A Validated UHPLC-Tandem Mass Spectrometry Method for Quantitative Analysis of Flavonolignans in Milk Thistle (Silybum marianum) Extracts 2016 51 Validated methods are needed for the analysis of natural product secondary metabolites. These methods are particularly important to translate in vitro observations to in vivo studies. Herein, a method is reported for the analysis of the key secondary...
Verticillin A Inhibits Leiomyosarcoma and Malignant Peripheral Nerve Sheath Tumor Growth Via Induction of Apoptosis 2016 55 Objective: The heterogeneity of soft tissue sarcoma (STS) represents a major challenge for the development of effective therapeutics. Comprised of over 50 different histology subtypes of various etiologies, STS subsets are further characterized as ei...
w-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation 2015 846 Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, as they may limit pathogenesis and increase bacterial susceptibil...
Waol A, trans-dihydrowaol A, and cis-dihydrowaol A: polyketide-derived (gamma)-lactones from a Volutella species 2013 791 An organic extract of a filamentous fungus (MSX 58801), identified as a Volutella sp. (Hypocreales, Ascomycota), displayed moderate cytotoxic activity against NCI-H460 human large cell lung carcinoma. Bioactivity-directed fractionation led to the iso...
The warfarin–cranberry juice interaction revisited: A systematic in vitro–in vivo evaluation 2010 1536 Background: Cranberry products have been implicated in several case reports to enhance the anticoagulant effect of warfarin. The mechanism could involve inhibition of the hepatic CYP2C9-mediated metabolic clearance of warfarin by components in cranbe...