new strategy aimed at finding drugs to treat neglected infectious

With an unconventional approach they have designed, from the University of Pittsburgh Drug Discovery and her staff at Walter Reed Army Institute of Research to identify promising compounds for the treatment of leishmaniasis, a parasitic infection, which by many as one of the most neglected diseases in the world. Results are available online today in the journal PLoS Neglected Tropical Diseases. These drug candidates are worrying that may grow to a certain stage in the lifecycle of the parasite, were discovered by screening approximately 200,000 compounds, and then merging them into chemotypes or chemical classes, both new and familiar, said Senior Investigator John S. Lazo, Ph.D., director of Pitt Drug Discovery Institute, and Allegheny Foundation Professor in the Department of Pharmacology and Chemical Biology, Pitt School of Medicine. One of the strongest links was tested in a mouse model of leishmaniasis, confirming it could effectively against infection.

"We're making real progress in our efforts to cope with new drugs that I could find the best neglected of neglected diseases," said Lazo. "And the method we have developed could be applied to treatments for other parasitic infections, which are an enormous burden on global health to be found. "

According to the U. S. Centers for Disease Control and Prevention, everyone in the world years ago about 1.5 million new cases of cutaneous leishmaniasis of the skin infection that causes ulcers and visceral than 500,000 infections leading to fever, weight loss and enlargement of the spleen and liver. There is no vaccine or drug against the parasitic infection that is transmitted by sandflies, biting prevent.

At an interest in developing new therapies for the treatment of leishmaniasis, because the military presence in Afghanistan and Iraq, where infections are the result of growth, "said co-investigator Colonel Alan Magill, MD, Director of the Division of Experimental Therapeutics at Walter Reed Army Institute of Research, Silver Spring, Maryland

"Our soldiers are capable of being at risk of infection by the parasite Leishmania, but the treatment we have to produce serious side effects, he said. "In addition, the body becomes resistant to these drugs have not changed in 50 years."

For this new study, took the lead researcher Elizabeth R. Sharlow, Ph.D., research assistant professor in Pitt's School of Medicine Department of Pharmacology and Chemical Biology, unconventional approaches to drug candidates to find. First, they developed a test based on the life cycle of Leishmania promastigote stage that the infected sand fly, to measure the candidate's ability to inhibit the parasite.

"Another step was unusual to screen compounds with relatively high concentrations, they tend promastigote growth would be affected," said Dr. Sharlow. "The objective was to compare the diversity of ingredients, which are then grouped into similar types of chemotherapy with high-performance methods of calculation, we have other tests to maximize more manageable."

Researchers have dubbed this process "hilum" for high throughput, low stringency, manufactured Enhanced Small Molecule Screening. Low stringency is the concept of discovery of new drugs for high concentration.

A promising compound against Leishmania they found proved disulfiram, or Antabuse, a drug that causes an acute sensitivity to alcohol and it is sometimes prescribed to prevent alcohol use among patients with alcoholism chronic. Tests in a mouse model of infection showed that it could slow growth promastigotes in a living organism, are once again demonstrating that the hilum can be an effective strategy, just as unpredictable drug candidates.

"In a million years would we be on the use of a compound such as disulfiram for leishmaniasis is not expected," said Lazo. "He calls because they are already widespread and cheap, but in its current form, it is perhaps not the best option to treat the infection. We want to continue to improve with our colleagues from Walter Reed to develop the compound and power efficiency. "

All data from primary screening and confirmation have been uploaded, added: "This is the data device identified by medical researchers and industry has earned around the world and other anti-leishmania refine candidates drugs, "said Dr.. Lazo. "And may be the same screening techniques is very valuable to find compounds to treat other parasites.