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2. Synthesis of Guaianolide Analogues with a Tunable α-Methylene−γ-lactam Electrophile and Correlating Bioactivity with Thiol Reactivity

Author

Matthew E. Cuellar, Daniel P Dempe, Kay M. Brummond, Paul A. Jackson, John C. Widen, Katherine F. M. Jones, Michael A. Walters, Henry A M Schares, Francois Grillet, and Daniel A. Harki

Subjects
Lactams, Cysteamine, Proof of Concept Study, 01 natural sciences, Article, Sesquiterpenes, Guaiane, 03 medical and health sciences, chemistry.chemical_compound, Chlorocebus aethiops, Drug Discovery, Animals, Humans, Molecule, Reactivity (chemistry), Methylene, Cytotoxicity, Vero Cells, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, NF-kappa B, Combinatorial chemistry, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, HEK293 Cells, chemistry, A549 Cells, Electrophile, Thiol, Lactam, Molecular Medicine, Lactone, Signal Transduction
Abstract

α-Methylene-γ-lactones are present in ∼3% of known natural products, and compounds comprising this motif display a range of biological activities. However, this reactive lactone limits informed structure-activity relationships for these bioactive molecules. Herein, we describe chemically tuning the electrophilicity of the α-methylene-γ-lactone by replacement with an α-methylene-γ-lactam. Guaianolide analogues having α-methylene-γ-lactams are synthesized using the allenic Pauson-Khand reaction. Substitution of the lactam nitrogen with electronically different groups affords diverse thiol reactivity. Cellular NF-κB inhibition assays for these lactams were benchmarked against parthenolide and a synthetic α-methylene-γ-lactone showing a positive correlation between thiol reactivity and bioactivity. Cytotoxicity assays show good correlation at the outer limits of thiol reactivity but less so for compounds with intermediate reactivity. A La assay to detect reactive molecules by nuclear magnetic resonance and mass spectrometry peptide sequencing assays with the La antigen protein demonstrate that lactam analogues with muted nonspecific thiol reactivities constitute a better electrophile for rational chemical probe and therapeutic molecule design.

Published
2020
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3. Function-Oriented and Modular (+/-)-cis-Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF-κB Inhibitors

Author

Daniel A. Harki, Fabien Emmetiere, Alexander J. Grenning, Emily Bevan–Smith, Hendrik Luesch, Henry A M Schares, Katherine F. M. Jones, and Ranjala Ratnayake

Subjects
Biological Products, Natural product, 010405 organic chemistry, Stereochemistry, NF-E2-Related Factor 2, education, Organic Chemistry, Nrf2 activators, NF-kappa B, Nf κb inhibitors, General Chemistry, 010402 general chemistry, 01 natural sciences, humanities, Catalysis, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Michael reaction, Local environment, Function (biology), Biological evaluation
Abstract

Described herein is a function-oriented synthesis route and biological evaluation of pseudoguaianolide analogues. The 10-step synthetic route developed retains the topological complexity of the natural product, installs functional handles for late-stage diversification, and forges the key bioactive Michael acceptors early in the synthesis. The analogues were found to be low-micromolar Nrf2 activators and micromolar NF-κB inhibitors and dependent on the local environment of the Michael acceptor moieties.

Published
2021

5. Contempt for the Welsh

Author

F M Jones

Subjects
Wales, Contempt, Criminology, language.human_language, Welsh, England, language, Humans, Sociology, General Dentistry, Prejudice (legal term), Minority Groups, Prejudice, Language
Published
2005

6. Cooperative state-federal turkey ornithosis task force, Texas, 1974

Author

J W, Walker, K A, Hand, S E, Glass, F M, Jones, and L W, Pessarra

Subjects
Occupational Diseases, Turkeys, Animals, Humans, Food-Processing Industry, Psittacosis, Texas, Poultry Diseases
Abstract

Ornithosis was suggested by a routine analysis of tissue specimens from Texas turkey flocks submitted to the Texas AM University Poultry Disease Laboratory at Gonzales on April 30, 1974, and of subsequent specimens from four additional flocks. Subsequently, illness in humans at turkey processing plants in Texas, Nebraska, and Missouri, implicating turkeys from Texas, was confirmed as ornithosis in July 1974; and, associated with this outbreak, ornithosis was suspected as the cause of the death of one human. Action was taken by state and federal poultry disease control and inspection officials, public health agencies, and the turkey industry in Texas.

Published
1976

7. Nur-i-Afshan V.59 no.03 January 1931

Author

Belly, A. R.; Najamuddin, F. M.; Jones, Bevan; Jalaluddin; Ogdon, J., Paul, S. M., Belly, A. R.; Najamuddin, F. M.; Jones, Bevan; Jalaluddin; Ogdon, J., and Paul, S. M.

Abstract

Contents: Shiʻr o suḵẖan : jaz̲bāt-i shifā [Poetry] by Bīle, Ae. Ār. - Masīḥī īmān aur ʻamal : jamāʻtī duʻā [Article] - Jhūṭe masīḥīyūn̲ kī pahcān [Article] - Murāsalāt [Letter] - Āmad-i s̲ānī ḥukam-i rabbānī [Article] by Najmuddīn, Ef. Em. - Masīḥīyūn̲ ko Musalmānon̲ meṉ kis t̤arḥ masīḥiyat kī tablīg̲h̲ karnī cāhiʼe [Article] by Jonz, Bevan - K̲h̲udāvand merā caupān he mujhe kuch kamī nahīṉ [Article] by Jalāluddīn - Mausīqī-yi Hind par rīviyū - Din āgaʼe bahār ke [Article] by Augḍan, Je. - Aīk īrānī ṣāḥab kī dāstān keh voh kese islām ko k̲h̲airbād keh kar masīḥ ho gayā [Article] - Panjāb meṉ tilūṉ kī faṣal bābat 1930 kā āk̲h̲rī tak̲h̲mīnah [News] - Muk̲h̲talif k̲h̲abrain̲ [News] - Inṭarnashnal sabbat Skūl ke asabaq [Article] This volume of Nur-i-Afshan published weekly on Fridays from Lahore.

Published
1931

8. Local history cards for the Jones family

Author

Jones, A. G. F.; Jones, B.; Jones, Ad; Jones, Albert, 1861-; Jones, Alvina, 1874-; Jones, A.; Jones, Albert B.; Jones, Alphus, 1832-; Jones, Alfred, 1843-; Jones, Andrew, 1796-; Jones, Andrew, 1843-; Jones, Benjamin, 1811-1862; Jones, Bailes E.; Jones, Bewford; Jones, B.; Jones, Bartlet; Jones, Billy; Jones, Bluford; Jones, Charles; Jones, Charles, 1806-; Jones, David, 1854-; Jones, David; Jones, Daniel; Jones, David H.; Jones, David L.; Jones, David W., 1824-1893; Jones, David, 1830-; Jones, Dinah; Jones, Edward; Jones, Ellis; Jones, Ellen; Jones, Elizabeth, 1813-; Andes, Elizabeth; Jones, Elizabeth, 1780-; Jones, Elizabeth, 1776-1852; Jones, Emma, 1846-; Jones, Elizabeth, 1802-; Jones, Ellnarde, 1799-; Jones, F. M.; Jones, Francis, 1820-; Jones, George, 1842-; Jones, George W., 1837-; Jones, George A., 1866-; Jones, George W.; Jones, George R., 1858-; Jones, George W., 1859-; Jones, Gilbert, 1788-1883; Jones, Greenbury; Jones, Henry A., 1829-; Jones, Higer, 1857-; Jones, Henry, 1832-; Jones, Henry, 1804-; Jones, Henry A., 1828-; Jones, Hutson; Jones, Isaac, 1827-; Jones, Isaac, 1849-; Jones, Isaac, -1833; Jones, J. W., 1852-; Jones, Jabesh; Jones, Jacob; Jones, Jacob W.; Jones, Jacob, 1797-; Jones, Jacob, 1800-1889; Jones, Jacob, 1805-; Jones, Jacob, 1806-1891; Jones, Jacob F., 1831-; Jones, Jacob J., 1863-; Jones, James; Jones, James, -1843; Jones, James H.; Jones, James, 1796-1860; Jones, James D., 1840-1864; Jones, James, 1801-; Jones, James H., 1819-; Jones, James M., 1779-1845; Jones, Jimmy, -1860; Jones, Job S.; Jones, John, 1810-; Jones, John D.; Jones, John; Jones, John W.; Jones, John A.; Jones, John, 1808-1881; Jones, John D., 1809-1870; Jones, John, 1810-; Jones, John, 1816-; Jones, John, 1821-; Jones, John, 1835-; Jones, John W., 1846-; Jones, John, 1839-; Jones, John M., 1857-; Jones, Joseph; Jones, Joseph, 1834-; Jones, Joshua, 1836-; Jones, Laodicea, 1808-; Jones, L. S.; Jones, Levi, 1808-; Jones, Leach; Jones, Levi, 1834-; Jones, Levi J., 1847-; Jo, Bennett, Elaine C., Jones, A. G. F.; Jones, B.; Jones, Ad; Jones, Albert, 1861-; Jones, Alvina, 1874-; Jones, A.; Jones, Albert B.; Jones, Alphus, 1832-; Jones, Alfred, 1843-; Jones, Andrew, 1796-; Jones, Andrew, 1843-; Jones, Benjamin, 1811-1862; Jones, Bailes E.; Jones, Bewford; Jones, B.; Jones, Bartlet; Jones, Billy; Jones, Bluford; Jones, Charles; Jones, Charles, 1806-; Jones, David, 1854-; Jones, David; Jones, Daniel; Jones, David H.; Jones, David L.; Jones, David W., 1824-1893; Jones, David, 1830-; Jones, Dinah; Jones, Edward; Jones, Ellis; Jones, Ellen; Jones, Elizabeth, 1813-; Andes, Elizabeth; Jones, Elizabeth, 1780-; Jones, Elizabeth, 1776-1852; Jones, Emma, 1846-; Jones, Elizabeth, 1802-; Jones, Ellnarde, 1799-; Jones, F. M.; Jones, Francis, 1820-; Jones, George, 1842-; Jones, George W., 1837-; Jones, George A., 1866-; Jones, George W.; Jones, George R., 1858-; Jones, George W., 1859-; Jones, Gilbert, 1788-1883; Jones, Greenbury; Jones, Henry A., 1829-; Jones, Higer, 1857-; Jones, Henry, 1832-; Jones, Henry, 1804-; Jones, Henry A., 1828-; Jones, Hutson; Jones, Isaac, 1827-; Jones, Isaac, 1849-; Jones, Isaac, -1833; Jones, J. W., 1852-; Jones, Jabesh; Jones, Jacob; Jones, Jacob W.; Jones, Jacob, 1797-; Jones, Jacob, 1800-1889; Jones, Jacob, 1805-; Jones, Jacob, 1806-1891; Jones, Jacob F., 1831-; Jones, Jacob J., 1863-; Jones, James; Jones, James, -1843; Jones, James H.; Jones, James, 1796-1860; Jones, James D., 1840-1864; Jones, James, 1801-; Jones, James H., 1819-; Jones, James M., 1779-1845; Jones, Jimmy, -1860; Jones, Job S.; Jones, John, 1810-; Jones, John D.; Jones, John; Jones, John W.; Jones, John A.; Jones, John, 1808-1881; Jones, John D., 1809-1870; Jones, John, 1810-; Jones, John, 1816-; Jones, John, 1821-; Jones, John, 1835-; Jones, John W., 1846-; Jones, John, 1839-; Jones, John M., 1857-; Jones, Joseph; Jones, Joseph, 1834-; Jones, Joshua, 1836-; Jones, Laodicea, 1808-; Jones, L. S.; Jones, Levi, 1808-; Jones, Leach; Jones, Levi, 1834-; Jones, Levi J., 1847-; Jo, and Bennett, Elaine C.

Abstract

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11. Evening Grosbeak in Eastern Virginia

Author

F. M. Jones

Subjects
Geography, Evening, biology, Animal Science and Zoology, biology.organism_classification, Archaeology, Ecology, Evolution, Behavior and Systematics, Grosbeak
Published
1947
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