Literature DB >> 31616928

A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites.

Rebecca L Clements1,2, Vincent Streva2, Peter Dumoulin3, Weigang Huang4, Edward Owens5, Dipak K Raj6, Barbara Burleigh3, Manuel Llinás5,7, Elizabeth A Winzeler8, Qisheng Zhang4, Jeffrey D Dvorin2,9.   

Abstract

Spreading antimalarial resistance threatens effective treatment of malaria, an infectious disease caused by Plasmodium parasites. We identified a compound, BCH070, that inhibits asexual growth of multiple antimalarial-resistant strains of Plasmodium falciparum (half maximal inhibitory concentration [IC50] = 1-2 µM), suggesting that BCH070 acts via a novel mechanism of action. BCH070 preferentially kills early ring-form trophozoites, and, importantly, equally inhibits ring-stage survival of wild-type and artemisinin-resistant parasites harboring the PfKelch13:C580Y mutation. Metabolomic analysis demonstrates that BCH070 likely targets multiple pathways in the parasite. BCH070 is a promising lead compound for development of new antimalarial combination therapy that retains activity against artemisinin-resistant parasites.
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Entities:  

Keywords:  zzm321990 Plasmodium falciparumzzm321990 ; antimalarial; artemisinin resistance; malaria; ring-stage survival

Mesh:

Substances:

Year:  2020        PMID: 31616928      PMCID: PMC7050989          DOI: 10.1093/infdis/jiz534

Source DB:  PubMed          Journal:  J Infect Dis        ISSN: 0022-1899            Impact factor:   5.226


  14 in total

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Authors:  Paul R Gilson; Cyrus Tan; Kate E Jarman; Kym N Lowes; Joan M Curtis; William Nguyen; Adrian E Di Rago; Hayley E Bullen; Boris Prinz; Sandra Duffy; Jonathan B Baell; Craig A Hutton; Helene Jousset Subroux; Brendan S Crabb; Vicky M Avery; Alan F Cowman; Brad E Sleebs
Journal:  J Med Chem       Date:  2017-01-26       Impact factor: 7.446

2.  The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs.

Authors:  Jonathan D Herman; Lauren R Pepper; Joseph F Cortese; Guillermina Estiu; Kevin Galinsky; Vanessa Zuzarte-Luis; Emily R Derbyshire; Ulf Ribacke; Amanda K Lukens; Sofia A Santos; Vishal Patel; Clary B Clish; William J Sullivan; Huihao Zhou; Selina E Bopp; Paul Schimmel; Susan Lindquist; Jon Clardy; Maria M Mota; Tracy L Keller; Malcolm Whitman; Olaf Wiest; Dyann F Wirth; Ralph Mazitschek
Journal:  Sci Transl Med       Date:  2015-05-20       Impact factor: 17.956

3.  Flow cytometry-based analysis of artemisinin-resistant Plasmodium falciparum in the ring-stage survival assay.

Authors:  Chanaki Amaratunga; Aaron T Neal; Rick M Fairhurst
Journal:  Antimicrob Agents Chemother       Date:  2014-05-27       Impact factor: 5.191

4.  Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates.

Authors:  Judith Straimer; Nina F Gnädig; Benoit Witkowski; Chanaki Amaratunga; Valentine Duru; Arba Pramundita Ramadani; Mélanie Dacheux; Nimol Khim; Lei Zhang; Stephen Lam; Philip D Gregory; Fyodor D Urnov; Odile Mercereau-Puijalon; Françoise Benoit-Vical; Rick M Fairhurst; Didier Ménard; David A Fidock
Journal:  Science       Date:  2014-12-11       Impact factor: 47.728

5.  Efficient site-specific integration in Plasmodium falciparum chromosomes mediated by mycobacteriophage Bxb1 integrase.

Authors:  Louis J Nkrumah; Rebecca A Muhle; Pedro A Moura; Pallavi Ghosh; Graham F Hatfull; William R Jacobs; David A Fidock
Journal:  Nat Methods       Date:  2006-08       Impact factor: 28.547

6.  Clonal viability measurements on Plasmodium falciparum to assess in vitro schizonticidal activity of leupeptin, chloroquine, and 5-fluoroorotate.

Authors:  R D Young; P K Rathod
Journal:  Antimicrob Agents Chemother       Date:  1993-05       Impact factor: 5.191

7.  Plasmodium falciparum transfected with ultra bright NanoLuc luciferase offers high sensitivity detection for the screening of growth and cellular trafficking inhibitors.

Authors:  Mauro F Azevedo; Catherine Q Nie; Brendan Elsworth; Sarah C Charnaud; Paul R Sanders; Brendan S Crabb; Paul R Gilson
Journal:  PLoS One       Date:  2014-11-13       Impact factor: 3.240

8.  A broad analysis of resistance development in the malaria parasite.

Authors:  Victoria C Corey; Amanda K Lukens; Eva S Istvan; Marcus C S Lee; Virginia Franco; Pamela Magistrado; Olivia Coburn-Flynn; Tomoyo Sakata-Kato; Olivia Fuchs; Nina F Gnädig; Greg Goldgof; Maria Linares; Maria G Gomez-Lorenzo; Cristina De Cózar; Maria Jose Lafuente-Monasterio; Sara Prats; Stephan Meister; Olga Tanaseichuk; Melanie Wree; Yingyao Zhou; Paul A Willis; Francisco-Javier Gamo; Daniel E Goldberg; David A Fidock; Dyann F Wirth; Elizabeth A Winzeler
Journal:  Nat Commun       Date:  2016-06-15       Impact factor: 14.919

9.  Cyclization-blocked proguanil as a strategy to improve the antimalarial activity of atovaquone.

Authors:  Tina S Skinner-Adams; John H Ryan; Katherine T Andrews; Gillian M Fisher; Andrew G Riches; Oliver E Hutt; Karen E Jarvis; Tony Wilson; Mark von Itzstein; Pradeep Chopra; Yevgeniya Antonova-Koch; Stephan Meister; Elizabeth A Winzeler; Mary Clarke; David A Fidock; Jeremy N Burrows
Journal:  Commun Biol       Date:  2019-05-03

10.  Targeting Plasmodium PI(4)K to eliminate malaria.

Authors:  Case W McNamara; Marcus Cs Lee; Chek Shik Lim; Siau Hoi Lim; Jason Roland; Oliver Simon; Bryan Ks Yeung; Arnab K Chatterjee; Susan L McCormack; Micah J Manary; Anne-Marie Zeeman; Koen J Dechering; Tr Santha Kumar; Philipp P Henrich; Kerstin Gagaring; Maureen Ibanez; Nobutaka Kato; Kelli L Kuhen; Christoph Fischli; Advait Nagle; Matthias Rottmann; David M Plouffe; Badry Bursulaya; Stephan Meister; Lucia Rameh; Joerg Trappe; Dorothea Haasen; Martijn Timmerman; Robert W Sauerwein; Rossarin Suwanarusk; Bruce Russell; Laurent Renia; Francois Nosten; David C Tully; Clemens Hm Kocken; Richard J Glynne; Christophe Bodenreider; David A Fidock; Thierry T Diagana; Elizabeth A Winzeler
Journal:  Nature       Date:  2013-11-27       Impact factor: 49.962

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  1 in total

1.  Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice.

Authors:  Katelyn Vendrely Brenneman; Xue Li; Sudhir Kumar; Elizabeth Delgado; Lisa A Checkley; Douglas A Shoue; Ann Reyes; Biley A Abatiyow; Meseret T Haile; Rupam Tripura; Tom Peto; Dysoley Lek; Katrina A Button-Simons; Stefan H I Kappe; Mehul Dhorda; François Nosten; Standwell C Nkhoma; Ian H Cheeseman; Ashley M Vaughan; Michael T Ferdig; Tim J C Anderson
Journal:  iScience       Date:  2022-03-16
  1 in total

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