Literature DB >> 15673744

Provitamin B5 (pantothenol) inhibits growth of the intraerythrocytic malaria parasite.

Kevin J Saliba1, Isabelle Ferru, Kiaran Kirk.   

Abstract

Pantothenic acid, a precursor of the crucial enzyme cofactor coenzyme A, is one of a relatively few nutrients for which the intraerythrocytic parasite has an absolute and acute requirement from the external medium. In some organisms the provitamin pantothenol can serve as a source of pantothenic acid; however, this was not the case for the human malaria parasite Plasmodium falciparum. Instead, pantothenol inhibited the in vitro growth of P. falciparum via a mechanism that involves competition with pantothenate and which can be attributed to inhibition of the parasite's pantothenate kinase. Oral administration of pantothenol to mice infected with the murine parasite Plasmodium vinckei vinckei resulted in a significant inhibition of parasite proliferation. This study highlights the potential of the coenzyme A biosynthesis pathway in general, and pantothenate kinase in particular, as an antimalarial drug target.

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Year:  2005        PMID: 15673744      PMCID: PMC547364          DOI: 10.1128/AAC.49.2.632-637.2005

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN: 0066-4804            Impact factor:   5.191


  22 in total

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Journal:  J Vitaminol (Kyoto)       Date:  1969-03-10

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Journal:  Biochem Biophys Res Commun       Date:  1999-07-05       Impact factor: 3.575

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Journal:  J Biol Chem       Date:  2003-11-20       Impact factor: 5.157

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  21 in total

Review 1.  Vitamin and cofactor biosynthesis pathways in Plasmodium and other apicomplexan parasites.

Authors:  Sylke Müller; Barbara Kappes
Journal:  Trends Parasitol       Date:  2007-02-02

2.  A pantetheinase-resistant pantothenamide with potent, on-target, and selective antiplasmodial activity.

Authors:  Cristiano J Macuamule; Erick T Tjhin; Collins E Jana; Leanne Barnard; Lizbé Koekemoer; Marianne de Villiers; Kevin J Saliba; Erick Strauss
Journal:  Antimicrob Agents Chemother       Date:  2015-04-06       Impact factor: 5.191

3.  Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity.

Authors:  Annabelle Hoegl; Hamed Darabi; Elisa Tran; Emelia Awuah; Eleanor S C Kerdo; Eric Habib; Kevin J Saliba; Karine Auclair
Journal:  Bioorg Med Chem Lett       Date:  2014-06-18       Impact factor: 2.823

4.  A class of pantothenic acid analogs inhibits Plasmodium falciparum pantothenate kinase and represses the proliferation of malaria parasites.

Authors:  Christina Spry; Christina L L Chai; Kiaran Kirk; Kevin J Saliba
Journal:  Antimicrob Agents Chemother       Date:  2005-11       Impact factor: 5.191

5.  Triazole Substitution of a Labile Amide Bond Stabilizes Pantothenamides and Improves Their Antiplasmodial Potency.

Authors:  Vanessa M Howieson; Elisa Tran; Annabelle Hoegl; Han Ling Fam; Jonathan Fu; Kate Sivonen; Xiao Xuan Li; Karine Auclair; Kevin J Saliba
Journal:  Antimicrob Agents Chemother       Date:  2016-11-21       Impact factor: 5.191

6.  Structural modification of pantothenamides counteracts degradation by pantetheinase and improves antiplasmodial activity.

Authors:  Marianne de Villiers; Cristiano Macuamule; Christina Spry; Yoo-Min Hyun; Erick Strauss; Kevin J Saliba
Journal:  ACS Med Chem Lett       Date:  2013-06-17       Impact factor: 4.345

7.  The human malaria parasite Plasmodium falciparum is not dependent on host coenzyme A biosynthesis.

Authors:  Christina Spry; Kevin J Saliba
Journal:  J Biol Chem       Date:  2009-07-07       Impact factor: 5.157

8.  Identification and functional analysis of the primary pantothenate transporter, PfPAT, of the human malaria parasite Plasmodium falciparum.

Authors:  Yoann Augagneur; Lise Jaubert; Matthieu Schiavoni; Niseema Pachikara; Aprajita Garg; Sahar Usmani-Brown; Donna Wesolowski; Skye Zeller; Abhisek Ghosal; Emmanuel Cornillot; Hamid M Said; Priti Kumar; Sidney Altman; Choukri Ben Mamoun
Journal:  J Biol Chem       Date:  2013-05-31       Impact factor: 5.157

9.  Novel pantothenate derivatives for anti-malarial chemotherapy.

Authors:  Helmi E Pett; Patrick A M Jansen; Pedro H H Hermkens; Peter N M Botman; Christien A Beuckens-Schortinghuis; Richard H Blaauw; Wouter Graumans; Marga van de Vegte-Bolmer; Karin M J Koolen; Floris P J T Rutjes; Koen J Dechering; Robert W Sauerwein; Joost Schalkwijk
Journal:  Malar J       Date:  2015-04-18       Impact factor: 2.979

10.  Pantothenamides are potent, on-target inhibitors of Plasmodium falciparum growth when serum pantetheinase is inactivated.

Authors:  Christina Spry; Cristiano Macuamule; Zhiyang Lin; Kristopher G Virga; Richard E Lee; Erick Strauss; Kevin J Saliba
Journal:  PLoS One       Date:  2013-02-06       Impact factor: 3.240

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