Tyler Graf

There are 36 included publications by Tyler Graf :

TitleDateViewsBrief Description
Benzoquinones and Terphenyl Compounds As Phosphodiesterase-4B Inhibitors from a Fungus of the Order Chaetothyriales (MSX 47445) 2013 1985 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...
Biosynthesis of Fluorinated Peptaibols Using a Site-Directed Building Block Incorporation Approach 2017 1172 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 779 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...
Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions 2020 1361 The safety and efficacy of kratom (Mitragyna speciosa) for treatment of pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on just two of these, mitragynine and 7-hydroxymitragynin...
Comparison of the chemistry and diversity of endophytes isolated from wild-harvested and greenhouse-cultivated yerba mansa (Anemopsis californica) 2015 1669 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 1444 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...
Conventional and Accelerated-Solvent Extractions of Green Tea (Camellia sinensis) for Metabolomics-Based Chemometrics 2017 1494 Metabolomics has emerged as an important analytical technique for multiple applications. The value of information obtained from metabolomics analysis depends on the degree to which the entire metabolome is present and the reliability of sample treatm...
Cyclodepsipeptides, Sesquiterpenoids, and Other Cytotoxic Metabolites from the Filamentous Fungus Trichothecium sp. (MSX 51320) 2011 1945 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 2362 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 2268 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...
Delitpyrones: a-Pyrone Derivatives from a Freshwater Delitschia sp. 2018 1456 In research focused on the discovery of new chemical diversity from freshwater fungi, a peak library was built and evaluated against a prostate cancer cell line, E006AA-hT, which was derived from an African American, as this population is disproporti...
Delivery of eupenifeldin via polymer-coated surgical buttresses prevents local lung cancer recurrence 2021 718 Lung cancer is the leading cause of cancer deaths worldwide. Unfortunately, high recurrence rates and poor survival remain despite surgical resection and conventional chemotherapy. Local drug delivery systems are a promising intervention for lung can...
Dereplication of Macrocyclic Trichothecenes from Extracts of Filamentous Fungi through UV and NMR Profiles 2010 2640 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 ...
Differential In Vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation 2011 2260 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...
Diterpene glycosides from Egletes Viscosa 2005 1936 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...
Enhanced Bioactivity of silybin B methylation Products 2013 1892 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...
Ethanolic Echinacea purpurea Extracts Contain a Mixture of Cytokine-Suppressive and Cytokine-Inducing Compounds, Including Some That Originate from Endophytic Bacteria 2015 2743 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...
Flavonolignans from Aspergillus iizukae, a Fungal Endophyte of Milk Thistle (Silybum marianum) 2014 2532 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...
Hepatic organic anion transporting polypeptides mediate disposition of milk thistle flavonolignans and pharmacokinetic silymarin-drug interactions 2021 263 Silybum marianum (L.) Gaertn. (Asteraceae), commonly known as milk thistle, is a botanical natural product used to self-treat multiple diseases such as Type 2 diabetes mellitus and nonalcoholic steatohepatitis (NASH). An extract from milk thistle see...
HiFSA Fingerprinting Applied to Isomers with Near-Identical NMR Spectra: The Silybin/Isosilybin Case 2013 1747 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 2174 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...
Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) using Human Intestinal Microsomes 2010 3339 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...
Large-Scale Isolation of Flavonolignans from Silybum marianum Extract Affords New Minor Constituents and Preliminary Structure-Activity Relationships 2010 951 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...
A Mass Spectrometry-Based Assay for Improved Quantitative Measurements of Efflux Pump Inhibition 2015 2339 Bacterial efflux pumps are active transport proteins responsible for resistance to selectedbiocides and antibiotics. It has been shown that production of efflux pumps is up-regulatedin a number of highly pathogenic bacteria, including methicillin res...
Milk thistle and prostate cancer: Differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. 2005 2452 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...
Multiple Effects of Silymarin on the Hepatitis C Virus Lifecycle 2010 2242 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...
Obionin B: an o-pyranonaphthoquinone decaketide from an unidentified fungus (MSX 63619) from the order Pleosporales 2011 1607 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...
Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction 2014 1662 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 ...
Prealamethicin F50 and Related Peptaibols from Trichoderma arundinaceum: Validation of their Authenticity via in situ Chemical Analysis 2017 1205 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...
Resorcylic Acid Lactones with Cytotoxic and NF-KB Inhibitory Activities and Their Structure–Activity Relationships 2011 2016 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...
Sarothrin from Alkanna orientalis Is an Antimicrobial Agent and Efflux Pump Inhibitor 2013 2271 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...
Semisynthesis, Cytotoxicity, Antiviral Activity, and Drug Interaction Liability of 7-O-methylated Analogues of Flavonolignans from Milk Thistle 2013 2603 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...
Silymarin Inhibits in Vitro T Cell Proliferation and Cytokine Production in Hepatitis C Virus Infection 2010 423 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...
Synergy-Directed Fractionation of Botanical Medicines: A Case Study with Goldenseal (Hydrastis canadensis) 2011 2458 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 440 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...
A Validated UHPLC-Tandem Mass Spectrometry Method for Quantitative Analysis of Flavonolignans in Milk Thistle (Silybum marianum) Extracts 2016 1580 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...