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Full-Text Articles in Natural Products Chemistry and Pharmacognosy

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave Jan 2025

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …


Anti-Inflammatory Potential Of Black Cumin Seed Oil And Its Nanoemulsion Formulation Against Lipopolysaccharide-Induced Liver Injury In Mice, Shady Swidan, Hesham Hafez, Rehab Hosni, Hatem Amin Dec 2024

Anti-Inflammatory Potential Of Black Cumin Seed Oil And Its Nanoemulsion Formulation Against Lipopolysaccharide-Induced Liver Injury In Mice, Shady Swidan, Hesham Hafez, Rehab Hosni, Hatem Amin

Pharmacy

Original Article

Anti-inflammatory potential of black cumin seed oil and its nanoemulsion formulation against lipopolysaccharide-induced liver injury in mice

Haffez, Hesham1,2,✉; Hosni, Rehab3; Swidan, Shady A.4; Amin, Hatem K.1,5

Author Information

1Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, 11795, Cairo, Egypt

2Center of Scientific Excellence “Helwan Structural Biology Research”, Helwan University, Helwan, 11795, Cairo, Egypt

3El Sisi Comprehensive Clinic, General Authority for Health Insurance-Giza, Haram, 12556, Giza, Egypt

4Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk, 11837, Cairo, …


Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods Jan 2023

Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods

Theses and Dissertations--Pharmacy

Antibiotic resistance happens when bacteria develop the ability to survive medications that normally terminate them. Instead, these super germs are able to survive in the body and produce a community of antibiotic resistance germs which can cause human fatalities. It is important to discover and develop new compounds and molecules that will improve this clinical obstacle. This research focused on analyzing the biosynthesis that incorporates distinctive chemical characteristic of various nucleoside antibiotics, ß-hydroxy amino acids and α-methyl-amino acids. ß-hydroxy amino acids and α-methyl-amino acids are considered an important class of industrially useful compounds, particularly for pharmaceutical development, and are found …


Complexation Of Glycoalkaloid Α- Tomatine With Sterols And Its Potential Application As An Anti-Cancer Drug, Bishal Nepal Jul 2021

Complexation Of Glycoalkaloid Α- Tomatine With Sterols And Its Potential Application As An Anti-Cancer Drug, Bishal Nepal

Dissertations

Glycoalkaloids (GAs) are secondary metabolites found mostly in higher plant species and some marine invertebrates. They are known to form complexes with 3β-hydroxy sterols such as cholesterol causing membrane disruption. So far the visual evidence showcasing the complexes formed between glycoalkaloids and sterols has been mainly restricted to some earlier studies using Brewster angle microscopy. This study aimed to develop a method for topographic and morphological analysis of sterol-glycoalkaloid complexes. Langmuir-Blodgett (LB) transfer of monolayers comprising of glycoalkaloid tomatine, sterols, and lipids in varying molar ratios onto mica followed by AFM examination was performed. The AFM method used required minimal …


Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed Mar 2019

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 …


The Value Of Universally Available Raw Nmr Data For Transparency, Reproducibility, And Integrity In Natural Product Research., James B. Mcalpine, Shao-Nong Chen, Andrei Kutateladze, John B. Macmillan, Giovanni Appendino, Andersson Barison, Mehdi A. Beniddir, Maique W. Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S. Butler, Robert J. Capon, Young H. Choi, David Coppage, Phillip Crews, Michael T. Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M. Egan, Mary J. Garson, Grégory Genta-Jouve, William H Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M. Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G. I. Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G Linington, Miaomiao Liu, Kerry L Mcphail, Tadeusz F Molinski, Bradley S Moore, Joo-Won Nam, Ram P Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H Oberlies, Fernanda M M Ocampos, Guohui Pan, Ronald J Quinn, D Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M Saunders, Thomas J Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M Williams, Philip G Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C Lankin, Jonathan Bisson, Guido F Pauli Jan 2019

The Value Of Universally Available Raw Nmr Data For Transparency, Reproducibility, And Integrity In Natural Product Research., James B. Mcalpine, Shao-Nong Chen, Andrei Kutateladze, John B. Macmillan, Giovanni Appendino, Andersson Barison, Mehdi A. Beniddir, Maique W. Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S. Butler, Robert J. Capon, Young H. Choi, David Coppage, Phillip Crews, Michael T. Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M. Egan, Mary J. Garson, Grégory Genta-Jouve, William H Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M. Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G. I. Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G Linington, Miaomiao Liu, Kerry L Mcphail, Tadeusz F Molinski, Bradley S Moore, Joo-Won Nam, Ram P Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H Oberlies, Fernanda M M Ocampos, Guohui Pan, Ronald J Quinn, D Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M Saunders, Thomas J Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M Williams, Philip G Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C Lankin, Jonathan Bisson, Guido F Pauli

Natural Sciences and Mathematics | Faculty Scholarship

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data …


Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber Jan 2019

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …


The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A. Valeriote, Phillip Crews Jan 2018

The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A. Valeriote, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

Our quest to isolate and characterize natural products with in vitro solid tumor selectivity is driven by access to repositories of Indo-Pacific sponge extracts. In this project an extract of a species of Haplosclerida sponge obtained from the US NCI Natural Products Repository displayed, by in vitro disk diffusion assay (DDA) and IC


Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui Jan 2018

Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui

Theses and Dissertations--Pharmacy

New antibiotics with novel targets or mechanisms of action are needed to counter the steady emergence of bacterial pathogens that are resistant to antibiotics used in the clinic. MraY, a promising novel target for antibiotic development, initiates the lipid cycle for the biosynthesis of peptidoglycan cell wall, which is essential for the survival of most, if-not-all, bacteria. MraY is an enzyme that catalyzes the transfer and attachment of phospho-MurNAc-pentapeptide to a lipid carrier, undecaprenylphosphate. Muraymycins are recently discovered lipopeptidyl nucleoside antibiotics that exhibit remarkable antibiotic activity against Gram-positive as well as Gram-negative bacteria by inhibiting MraY. We conducted a thorough …


Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews Mar 2017

Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS2 runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid …


Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle Jan 2016

Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle

Articles

Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, …


Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen Jan 2015

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …


Investigating Structure And Protein-Protein Interactions Of Key Post-Type Ii Pks Tailoring Enzymes, Theresa E. Downey Jan 2014

Investigating Structure And Protein-Protein Interactions Of Key Post-Type Ii Pks Tailoring Enzymes, Theresa E. Downey

Theses and Dissertations--Pharmacy

Type II polyketide synthase (PKS) produced natural products have proven to be an excellent source of pharmacologically relevant molecules due to their rich biological activities and chemical scaffolds. Type II-PKS manufactured polyketides share similar polycyclic aromatic backbones leaving their diversity to stem from various chemical additions and alterations facilitated by post-PKS tailoring enzymes. Evidence suggests that post-PKS tailoring enzymes form complexes in order to facilitate the highly orchestrated process of biosynthesis. Thus, protein-protein interactions between these enzymes must play crucial roles in their structures and functions. Despite the importance of these interactions little has been done to study them. In …


Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C. Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L. Mooberry Apr 2013

Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C. Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L. Mooberry

Natural Sciences and Mathematics | Faculty Scholarship

Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent …


Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F. Bjeldanes, Keith Rayburn Jan 2013

Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F. Bjeldanes, Keith Rayburn

Natural Sciences and Mathematics | Faculty Scholarship

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …


Development And Validation Of A Simple Method For The Detection Of Fascaplysin In Plasma, Kenneth H. Swartz, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Karen Tenney, Phillip Crews, Jiajiu Shaw Oct 2012

Development And Validation Of A Simple Method For The Detection Of Fascaplysin In Plasma, Kenneth H. Swartz, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Karen Tenney, Phillip Crews, Jiajiu Shaw

Natural Sciences and Mathematics | Faculty Scholarship

Fascaplysin is a cytotoxic natural product isolated from a variety of Indo-Pacific marine organisms, primarily Fascaplysinopsis sponges and Didemnum tunicates. Positive xenograft studies involving this alkaloid structural class have indicated that fascaplysin may serve as an important lead compound for preclinical development. This study was undertaken as a prelude to a full pharmacokinetics and therapeutic assessment of fascaplysin. We describe here a simple plasma preparation and a rapid HPLC method for the detection of fascaplysin in mice. The method was validated by parameters including good linear correlation, a limit of quantification of 107.1 μg/ mL, and a good precision with …


Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M. Vaske, Kimberly N. White, Tanya L. Cohen, Helene C. Vervoort, Karen Tenney, Frederick A. Valeriote, Leonard F. Bjeldanes, Phillip Crews Jul 2012

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M. Vaske, Kimberly N. White, Tanya L. Cohen, Helene C. Vervoort, Karen Tenney, Frederick A. Valeriote, Leonard F. Bjeldanes, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …


Enantioselective Demethylation: The Key To The Nornicotine Enantiomeric Composition In Tobacco Leaf, Bin Cai Jan 2012

Enantioselective Demethylation: The Key To The Nornicotine Enantiomeric Composition In Tobacco Leaf, Bin Cai

Theses and Dissertations--Plant and Soil Sciences

Nicotine and nornicotine are the two main alkaloids that accumulate in Nicotiana tabacum L. (tobacco), and nornicotine is the N-demethylation metabolite of nicotine. Nicotine is synthesized in the root, and probably primarily in the root tip. Both nicotine and nornicotine exist as two isomers that differ from each other by the orientation of H atom at the C-2' position on the pyrrolidine ring. (S)-nicotine is the dominant form in tobacco leaf and the enantiomer fraction of nicotine (EFnic), the fraction of (R)-enantiomer over the total nicotine, is approximately 0.002. Despite considerable efforts to elucidate nicotine and nornicotine …


Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani Aug 2010

Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani

Department of Biological & Biomedical Sciences

Background: The objective of present study was to provide the pharmacological basis for the medicinal use of Morinda citrifolia Linn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R). Results: Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase …


The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou Aug 2010

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou

Natural Sciences and Mathematics | Faculty Scholarship

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …


Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews Mar 2010

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …


Antispasmodic And Vasodilator Activities Of Morinda Citrifolia Root Extract Are Mediated Through Blockade Of Voltage Dependent Calcium Channels, Anwarul Hassan Gilani, Saf-Ur-Rehman Mandukhail, Javeid Iqbal, Masoom Yasinzai, Nauman Aziz, Aslam Khan, Najeeb-Ur-Rehman Jan 2010

Antispasmodic And Vasodilator Activities Of Morinda Citrifolia Root Extract Are Mediated Through Blockade Of Voltage Dependent Calcium Channels, Anwarul Hassan Gilani, Saf-Ur-Rehman Mandukhail, Javeid Iqbal, Masoom Yasinzai, Nauman Aziz, Aslam Khan, Najeeb-Ur-Rehman

Department of Biological & Biomedical Sciences

Background: Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. Methods: Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract …


Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M. Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela Jan 2009

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M. Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Natural Sciences and Mathematics | Faculty Scholarship

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …


Rapid Enzyme-Linked Immunosorbent Assay For Detection Of The Algal Toxin Domoic Acid, R Wayne Litaker, Thomas N. Stewart, Bich-Thuy L. Eberhart, John C. Wekell, Vera L. Trainer, Raphael M. Kudela, Peter E. Miller, Alice Roberts, Cassandra Hertz, Tyler A. Johnson, Greg Frankfurter, G. Jason Smith, Astrid Schnetzer, Joe Schumacker, Jonnette L. Bastian, Anthony Odell, Patrick Gentien, Dominique Le Gal, D Ransom Hardison, Patricia A. Tester Jan 2008

Rapid Enzyme-Linked Immunosorbent Assay For Detection Of The Algal Toxin Domoic Acid, R Wayne Litaker, Thomas N. Stewart, Bich-Thuy L. Eberhart, John C. Wekell, Vera L. Trainer, Raphael M. Kudela, Peter E. Miller, Alice Roberts, Cassandra Hertz, Tyler A. Johnson, Greg Frankfurter, G. Jason Smith, Astrid Schnetzer, Joe Schumacker, Jonnette L. Bastian, Anthony Odell, Patrick Gentien, Dominique Le Gal, D Ransom Hardison, Patricia A. Tester

Natural Sciences and Mathematics | Faculty Scholarship

Domoic acid (DA) is a potent toxin produced by bloom-forming phytoplankton in the genus Pseudo-nitzschia, which is responsible for causing amnesic shellfish poisoning (ASP) in humans. ASP symptoms include vomiting, diarrhea, and in more severe cases confusion, loss of memory, disorientation, and even coma or death. This paper describes the development and validation of a rapid, sensitive, enzyme linked immunosorbent assay test kit for detecting DA using a monoclonal antibody. The assay gives equivalent results to those obtained using standard high performance liquid chromatography, fluorenylmethoxycarbonyl high performance liquid chromatography, or liquid chromatography—mass spectrometry methods. It has a linear range …


Discovery Of Platelet-Type 12-Human Lipoxygenase Selective Inhibitors By High-Throughput Screening Of Structurally Diverse Libraries., Joshua D. Deschamps, Jeffrey T. Gautschi, Stephanie Whitman, Tyler A. Johnson, Nadine C. Gassner, Phillip Crews, Theodore R. Holman Nov 2007

Discovery Of Platelet-Type 12-Human Lipoxygenase Selective Inhibitors By High-Throughput Screening Of Structurally Diverse Libraries., Joshua D. Deschamps, Jeffrey T. Gautschi, Stephanie Whitman, Tyler A. Johnson, Nadine C. Gassner, Phillip Crews, Theodore R. Holman

Natural Sciences and Mathematics | Faculty Scholarship

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors …


Chemical Constituents Of Desmos Dumosus, Roxb., Mazdida Sulaiman Jan 2001

Chemical Constituents Of Desmos Dumosus, Roxb., Mazdida Sulaiman

Student Works (2000-2009)

The chemical content of the 'leaves and bark of Des mos dumosus has been carried out in this study. The leaves yielded nine isoquinoline type of alkaloids and two flavones. The isoquinoline alkaloids isolated were pronuciferine 37, stepharine 39, nomuciferine 40, (-) - 3 - hydroxynomuciferine 41, norlirioferine 42, asimilobine 43, liriodenine 44, lysicamine 45 and O - methylmoschatoline 46. The flavones were 5 - hydroxy - 6,7 - dimethoxyflavone 47 and 5 - hydroxy - 7,8 - dimethoxyflavone 48. The same flavones, 47 and 48 and the alkaloids 45 and 46 were also present in the bark of this …