Featured Research

from universities, journals, and other organizations

Novel compounds for fighting against parasitic diseases

Date:
April 5, 2011
Source:
Heidelberg Institute for Theoretical Studies
Summary:
Parasites of the Trypanosomatidae family cause a number of serious human diseases. Researchers have now published the identification of novel anti-parasitic compounds targeting an enzyme unique to the parasites. These compounds are promising for the development of drugs with fewer side-effects than current medical treatments.

Virtual screening identifies non-folate compounds, including a CNS drug, as antiparasitic agents inhibiting pteridine reductase.
Credit: Ferrari et al.

Trypanosomatid parasites cause diseases like African sleeping sickness, Chagas' disease and leishmaniasis. Leishmaniasis affects about 12 million people worldwide, mostly in developing countries. Current drug treatments are inadequate due to drug toxicity and resistance.

Related Articles


Now, a group of European scientists has discovered new compounds that may help to fight these diseases more effectively. The project was carried out by research groups headed by Maria Paola Costi (University of Modena and Reggio Emilia, Italy), Rebecca Wade (HITS, Heidelberg Institute for Theoretical Studies, Germany) and Paul Michels (De Duve Institute , Belgium). It was supported by the Cassa di Risparmio di Modena Foundation. The research results have been published in the Journal of Medicinal Chemistry.

Trypanosomatids require folates and biopterins. These are reduced by the enzymes dihydrofolate reductase (DHFR) and pteridine reductase (PTR1). When DHFR is inhibited, DNA replication is impaired, resulting in cell death. However in trypanosomatids, PTR1 is overexpressed when DHFR is inhibited, and PTR1 can take on the role of DHFR by reducing folates, ensuring parasite survival. For the treatment of anti-parasitic diseases, it is thus necessary to block two metabolic pathways by simultaneously inhibiting DHFR and PTR1 by a single drug or a combination of two specific inhibitors. PTR1 is not present in humans and is thus an excellent target for the design of specific compounds that target the parasite.

In this project, the scientists used a virtual screening approach combined with experimental screening methodologies, to identify non-folate-like inhibitors of Leishmania PTR1. Optimization was performed in two rounds of structure-based drug design cycles to improve specificity for PTR1 and selectivity against human DHFR, resulting in 18 drug-like molecules with low micromolar affinities and high in-vitro specificity profiles. Assays of efficacy in cultured Leishmania cells showed six compounds that were active in combination with a DHFR inhibitor. One of these was also effective alone. Several of these compounds showed low toxicity profiles, and one of them is a known drug approved for treatment of diseases of the central nervous system, suggesting potential for label extension of this compound as an anti-parasitic drug candidate.


Story Source:

The above story is based on materials provided by Heidelberg Institute for Theoretical Studies. Note: Materials may be edited for content and length.


Journal Reference:

  1. Stefania Ferrari, Federica Morandi, Domantas Motiejunas, Erika Nerini, Stefan Henrich, Rosaria Luciani, Alberto Venturelli, Sandra Lazzari, Samuele Calò, Shreedhara Gupta, Veronique Hannaert, Paul A. M. Michels, Rebecca C. Wade, M. Paola Costi. Virtual Screening Identification of Nonfolate Compounds, Including a CNS Drug, as Antiparasitic Agents Inhibiting Pteridine Reductase. Journal of Medicinal Chemistry, 2011; 54 (1): 211 DOI: 10.1021/jm1010572

Cite This Page:

Heidelberg Institute for Theoretical Studies. "Novel compounds for fighting against parasitic diseases." ScienceDaily. ScienceDaily, 5 April 2011. <www.sciencedaily.com/releases/2011/04/110404084808.htm>.
Heidelberg Institute for Theoretical Studies. (2011, April 5). Novel compounds for fighting against parasitic diseases. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2011/04/110404084808.htm
Heidelberg Institute for Theoretical Studies. "Novel compounds for fighting against parasitic diseases." ScienceDaily. www.sciencedaily.com/releases/2011/04/110404084808.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins