Literature DB >> 32944138

Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition.

Zhenhua Wu1, Jean-Simon Suppo2, Sarka Tumova3, Jonathan Strope4, Fernando Bravo2, Melody Moy1, Ethan S Weinstein1, Cody J Peer4, William D Figg4, William J Chain1, Antonio M Echavarren2, David J Beech3, John A Beutler5.   

Abstract

Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
Copyright © 2020 American Chemical Society.

Entities:  

Year:  2020        PMID： 32944138      PMCID： PMC7488277          DOI： 10.1021/acsmedchemlett.0c00186

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  32 in total

1.  Asymmetric, protecting-group-free total synthesis of (-)-englerin A.

Authors:  Qianghui Zhou; Xiaofei Chen; Dawei Ma
Journal:  Angew Chem Int Ed Engl       Date:  2010-05-03       Impact factor: 15.336

2.  Enantioselective synthesis of (-)-englerins A and B.

Authors:  Kian Molawi; Nicolas Delpont; Antonio M Echavarren
Journal:  Angew Chem Int Ed Engl       Date:  2010-05-03       Impact factor: 15.336

3.  Total synthesis and biological evaluation of (-)-englerin A and B: synthesis of analogues with improved activity profile.

Authors:  Lea Radtke; Matthieu Willot; Hongyan Sun; Slava Ziegler; Stephanie Sauerland; Carsten Strohmann; Roland Fröhlich; Peter Habenberger; Herbert Waldmann; Mathias Christmann
Journal:  Angew Chem Int Ed Engl       Date:  2011-03-29       Impact factor: 15.336

4.  Chemical synthesis and biological evaluation of the englerin analogues.

Authors:  Kok Ping Chan; David Y-K Chen
Journal:  ChemMedChem       Date:  2011-01-18       Impact factor: 3.466

5.  Total synthesis and biological evaluation of (-)-9-deoxy-englerin A.

Authors:  Dmitry B Ushakov; Vaidotas Navickas; Markus Ströbele; Cäcilia Maichle-Mössmer; Florenz Sasse; Martin E Maier
Journal:  Org Lett       Date:  2011-03-17       Impact factor: 6.005

6.  Tonantzitlolone is a nanomolar potency activator of transient receptor potential canonical 1/4/5 channels.

Authors:  Hussein N Rubaiy; Melanie J Ludlow; Karsten Siems; Katherine Norman; Richard Foster; Dietmar Wolf; John A Beutler; David J Beech
Journal:  Br J Pharmacol       Date:  2018-06-28       Impact factor: 8.739

7.  (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels.

Authors:  Yasemin Akbulut; Hannah J Gaunt; Katsuhiko Muraki; Melanie J Ludlow; Mohamed S Amer; Alexander Bruns; Naveen S Vasudev; Lea Radtke; Matthieu Willot; Sven Hahn; Tobias Seitz; Slava Ziegler; Mathias Christmann; David J Beech; Herbert Waldmann
Journal:  Angew Chem Int Ed Engl       Date:  2015-02-23       Impact factor: 15.336

8.  Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

Authors:  Laura López-Suárez; Lorena Riesgo; Fernando Bravo; Tanya T Ransom; John A Beutler; Antonio M Echavarren
Journal:  ChemMedChem       Date:  2016-03-23       Impact factor: 3.466

Review 9.  Remarkable Progress with Small-Molecule Modulation of TRPC1/4/5 Channels: Implications for Understanding the Channels in Health and Disease.

Authors:  Aisling Minard; Claudia C Bauer; David J Wright; Hussein N Rubaiy; Katsuhiko Muraki; David J Beech; Robin S Bon
Journal:  Cells       Date:  2018-06-01       Impact factor: 6.600

10.  TRPC4/TRPC5 channels mediate adverse reaction to the cancer cell cytotoxic agent (-)-Englerin A.

Authors:  Sin Ying Cheung; Matthias Henrot; Mohammad Al-Saad; Matthias Baumann; Heiko Muller; Anke Unger; Hussein N Rubaiy; Ilka Mathar; Klaus Dinkel; Peter Nussbaumer; Bert Klebl; Marc Freichel; Baptiste Rode; Sebastian Trainor; Steven J Clapcote; Mathias Christmann; Herbert Waldmann; Syed Khawar Abbas; David J Beech; Naveen S Vasudev
Journal:  Oncotarget       Date:  2018-07-03
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  1 in total

1.  Biological Effects of Modifications of the Englerin A Glycolate.

Authors:  Sarath P D Seenadera; Sarah A Long; Rhone Akee; Gabriela Bermudez; Gregory Parsonage; Jonathan Strope; Cody Peer; W Douglas Figg; Kathlyn A Parker; David J Beech; John A Beutler
Journal:  ACS Med Chem Lett       Date:  2022-08-22       Impact factor: 4.632
  1 in total

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