# Identification of a novel putative inhibitor of the Plasmodium falciparum purine nucleoside phosphorylase: exploring the purine salvage pathway to design new antimalarial drugs

Identification of a novel putative inhibitor of the Plasmodium falciparum purine nucleoside... Malaria, a tropical parasitic disease caused by Plasmodium spp., continues to place a heavy social burden, with almost 200 million cases and more than 580,000 deaths per year. Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) can be targeted for antimalarial drug design since its inhibition kills malaria parasites both in vitro and in vivo. Although the currently known inhibitors of PfPNP, immucillins, are orally available and of low toxicity to animals and humans, to the best of our knowledge, none of these compounds has entered clinical trials for the treatment of malaria. Using a pharmacophore-based virtual screening coupled to a consensual molecular docking approach, we identified 59 potential PfPNP inhibitors that are predicted to be orally absorbed in a Caco-2 cell model. Although most of these compounds are predicted to have high plasma protein binding levels, poor water solubility (except for compound 25) and CYP3A4 metabolic stability (except for 4, 7 and 8), four structures (4, 7, 8 and 25) remain as potential leads because of their plausible interaction with a specific hydrophobic pocket of PfPNP, which would confer them higher selectivity for PfPNP over human PNP. Additionally, both predicted Gibbs free energies for binding and molecular dynamics suggest that compound 4 may form a more stable complex with PfPNP than 5 $$^{\prime }$$ ′ -methylthio-immucillin-H, a potent and selective inhibitor of PfPNP. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Diversity Springer Journals

# Identification of a novel putative inhibitor of the Plasmodium falciparum purine nucleoside phosphorylase: exploring the purine salvage pathway to design new antimalarial drugs

, Volume 21 (3) – May 18, 2017
19 pages

Loading next page...

/lp/springer_journal/identification-of-a-novel-putative-inhibitor-of-the-plasmodium-l4a30lgzfc
Publisher
Springer Journals
Copyright
Copyright © 2017 by Springer International Publishing Switzerland
Subject
Life Sciences; Biochemistry, general; Organic Chemistry; Polymer Sciences; Pharmacy
ISSN
1381-1991
eISSN
1573-501X
D.O.I.
10.1007/s11030-017-9745-8
Publisher site
See Article on Publisher Site

### Abstract

Malaria, a tropical parasitic disease caused by Plasmodium spp., continues to place a heavy social burden, with almost 200 million cases and more than 580,000 deaths per year. Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) can be targeted for antimalarial drug design since its inhibition kills malaria parasites both in vitro and in vivo. Although the currently known inhibitors of PfPNP, immucillins, are orally available and of low toxicity to animals and humans, to the best of our knowledge, none of these compounds has entered clinical trials for the treatment of malaria. Using a pharmacophore-based virtual screening coupled to a consensual molecular docking approach, we identified 59 potential PfPNP inhibitors that are predicted to be orally absorbed in a Caco-2 cell model. Although most of these compounds are predicted to have high plasma protein binding levels, poor water solubility (except for compound 25) and CYP3A4 metabolic stability (except for 4, 7 and 8), four structures (4, 7, 8 and 25) remain as potential leads because of their plausible interaction with a specific hydrophobic pocket of PfPNP, which would confer them higher selectivity for PfPNP over human PNP. Additionally, both predicted Gibbs free energies for binding and molecular dynamics suggest that compound 4 may form a more stable complex with PfPNP than 5 $$^{\prime }$$ ′ -methylthio-immucillin-H, a potent and selective inhibitor of PfPNP.

### Journal

Molecular DiversitySpringer Journals

Published: May 18, 2017

## You’re reading a free preview. Subscribe to read the entire article.

### DeepDyve is your personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month ### Explore the DeepDyve Library ### Search Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly ### Organize Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place. ### Access Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals. ### Your journals are on DeepDyve Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more. All the latest content is available, no embargo periods. DeepDyve ### Freelancer DeepDyve ### Pro Price FREE$49/month
\$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off