Literature DB >> 30590924

Chemical Synthesis Enables Structural Reengineering of Aglaroxin C Leading to Inhibition Bias for Hepatitis C Viral Infection.

Wenhan Zhang1, Shufeng Liu2, Rayelle I Maiga, Jerry Pelletier, Lauren E Brown1, Tony T Wang2, John A Porco1.   

Abstract

As a unique rocaglate (flavagline) natural product, aglaroxin C displays intriguing biological activity by inhibiting hepatitis C viral entry. To further elucidate structure-activity relationships and diversify the pyrimidinone scaffold, we report a concise synthesis of aglaroxin C utilizing a highly regioselective pyrimidinone condensation. We have prepared more than 40 aglaroxin C analogues utilizing various amidine condensation partners. Through biological evaluation of analogues, we have discovered two lead compounds, CMLD012043 and CMLD012044, which show preferential bias for the inhibition of hepatitis C viral entry vs translation inhibition. Overall, the study demonstrates the power of chemical synthesis to produce natural product variants with both target inhibition bias and improved therapeutic indexes.

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Year:  2019        PMID： 30590924      PMCID： PMC6583776          DOI： 10.1021/jacs.8b11477

Source DB:  PubMed          Journal:  J Am Chem Soc        ISSN： 0002-7863            Impact factor:   15.419


  65 in total

1.  Inhibitors of protein synthesis identified by a high throughput multiplexed translation screen.

Authors:  Olivia Novac; Anne-Sophie Guenier; Jerry Pelletier
Journal:  Nucleic Acids Res       Date:  2004-02-09       Impact factor: 16.971

2.  Imidoylketene: An ab Initio Study of Its Conformations and Reactions.

Authors:  Sihyun Ham; David M. Birney
Journal:  J Org Chem       Date:  1996-06-14       Impact factor: 4.354

3.  Enantioselective synthesis of the complex rocaglate (-)-silvestrol.

Authors:  Baudouin Gerard; Regina Cencic; Jerry Pelletier; John A Porco
Journal:  Angew Chem Int Ed Engl       Date:  2007       Impact factor: 15.336

4.  Enantioselective photocycloaddition mediated by chiral Brønsted acids: asymmetric synthesis of the rocaglamides.

Authors:  Baudouin Gerard; Sheharbano Sangji; Daniel J O'Leary; John A Porco
Journal:  J Am Chem Soc       Date:  2006-06-21       Impact factor: 15.419

5.  An efficient synthesis of risperidone via stille reaction: antipsychotic, 5-HT2, and dopamine-D2-antagonist.

Authors:  Dong-Myung Kim; Min-Seok Kang; Jeong Sook Kim; Jin-Hyun Jeong
Journal:  Arch Pharm Res       Date:  2005-09       Impact factor: 4.946

6.  From ketenimines to ketenes to quinolones: two consecutive pseudopericyclic events.

Authors:  Mateo Alajarín; María-Mar Ortín; Pilar Sánchez-Andrada; Angel Vidal; Delia Bautista
Journal:  Org Lett       Date:  2005-11-10       Impact factor: 6.005

7.  A biomimetic approach to the rocaglamides employing photogeneration of oxidopyryliums derived from 3-hydroxyflavones.

Authors:  Baudouin Gerard; Guilford Jones Ii; John A Porco
Journal:  J Am Chem Soc       Date:  2004-10-27       Impact factor: 15.419

8.  Virus-host cell interactions during hepatitis C virus RNA replication: impact of polyprotein expression on the cellular transcriptome and cell cycle association with viral RNA synthesis.

Authors:  Frank Scholle; Kui Li; Francis Bodola; Masanori Ikeda; Bruce A Luxon; Stanley M Lemon
Journal:  J Virol       Date:  2004-02       Impact factor: 5.103

9.  Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris.

Authors:  Bang Yeon Hwang; Bao-Ning Su; Heebyung Chai; Qiuwen Mi; Leonardus B S Kardono; Johar J Afriastini; Soedarsono Riswan; Bernard D Santarsiero; Andrew D Mesecar; Robert Wild; Craig R Fairchild; Gregory D Vite; William C Rose; Norman R Farnsworth; Geoffrey A Cordell; John M Pezzuto; Steven M Swanson; A Douglas Kinghorn
Journal:  J Org Chem       Date:  2004-05-14       Impact factor: 4.354

10.  Stereoselective synthesis of (+/-)-rocaglaol analogues.

Authors:  Kai Thede; Nicole Diedrichs; Jacques P Ragot
Journal:  Org Lett       Date:  2004-11-25       Impact factor: 6.005
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  7 in total

1.  Regiodivergent Photocyclization of Dearomatized Acylphloroglucinols: Asymmetric Syntheses of (-)-Nemorosone and (-)-6-epi-Garcimultiflorone A.

Authors:  Saishuai Wen; Jonathan H Boyce; Sunil K Kandappa; Jayaraman Sivaguru; John A Porco
Journal:  J Am Chem Soc       Date:  2019-07-02       Impact factor: 15.419

2.  Synthesis of Pyrrolopyrazinones by Construction of the Pyrrole Ring onto an Intact Diketopiperazine.

Authors:  Susanna K Maisto; Angela P Leersnyder; Gwyneth L Pudner; Jonathan R Scheerer
Journal:  J Org Chem       Date:  2020-06-30       Impact factor: 4.354

3.  Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors.

Authors:  Wenhan Zhang; Jennifer Chu; Andrew M Cyr; Han Yueh; Lauren E Brown; Tony T Wang; Jerry Pelletier; John A Porco
Journal:  J Am Chem Soc       Date:  2019-07-30       Impact factor: 15.419

Review 4.  Update on Phytochemical and Biological Studies on Rocaglate Derivatives from Aglaia Species.

Authors:  Garima Agarwal; Long-Sheng Chang; Djaja Doel Soejarto; A Douglas Kinghorn
Journal:  Planta Med       Date:  2021-03-30       Impact factor: 3.007

Review 5.  SFPH proteins as therapeutic targets for a myriad of diseases.

Authors:  Dong Wang; Redouane Tabti; Sabria Elderwish; Amel Djehal; Nora Chouha; Franck Pinot; Peng Yu; Canan G Nebigil; Laurent Désaubry
Journal:  Bioorg Med Chem Lett       Date:  2020-10-06       Impact factor: 2.823

6.  Heat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer.

Authors:  Oshrat Levi-Galibov; Hagar Lavon; Rina Wassermann-Dozorets; Meirav Pevsner-Fischer; Shimrit Mayer; Esther Wershof; Yaniv Stein; Lauren E Brown; Wenhan Zhang; Gil Friedman; Reinat Nevo; Ofra Golani; Lior H Katz; Rona Yaeger; Ido Laish; John A Porco; Erik Sahai; Dror S Shouval; David Kelsen; Ruth Scherz-Shouval
Journal:  Nat Commun       Date:  2020-12-07       Impact factor: 14.919

7.  Synthesis of cis-Oriented Vicinal Diphenylethylenes through a Lewis Acid-Promoted Annulation of Oxotriphenylhexanoates.

Authors:  Martin Kamlar; Elin Henriksson; Ivana Císařová; Marcus Malo; Henrik Sundén
Journal:  J Org Chem       Date:  2021-06-17       Impact factor: 4.354
  7 in total

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