More than 12 million people in 88 countries are infected with leishmaniasis, a parasitic disease spread by the bite of infected sand flies. Nearly 2 million new cases are reported and about 70,000 people die from the disease annually.
Researchers at the University of Illinois at Chicago have discovered that compounds derived from a natural product can be used in developing a new drug to treat the disease.
Despite a worsening global impact of this disease, little progress has been made toward the development of new chemotherapeutics against it, says Alan Kozikowski, professor and director of UIC's Drug Discovery Program and coordinator of the project.
Drugs compounded from the toxic metal antimony have been the first-line therapeutic option for more than 50 years.
"But antimonials may cause acute pancreatitis and cardiac arrhythmia and can sometimes lead to death," Kozikowski said. Only recently, he said, have novel agents been added to the therapeutic arsenal.
Leishmaniasis can be cutaneus, which causes skin sores that leave ugly scars, or visceral, which is 100 percent fatal if left untreated.
Visceral leishmaniasis has increased in recent years due to emerging co-infections with HIV, spreading the disease to the developed countries in North America and southern Europe, Kozikowski said. The disease is normally found in tropical regions, from the rain forests in Central and South America to deserts in West Asia.
To find a starting point from which to develop a better drug, UIC postdoctoral researchers Suresh Tipparaju and Marco Pieroni synthesized a chemical "library" of more than 100 diverse compounds and screened them for biological activity against the Leishmania parasite. They observed high antiparasitic activity in a compound first isolated from streptomyces bacteria more than 20 years ago. That compound, Tipparaju said, could potentially be modified to treat leishmaniasis. It was already three times more active than miltefosine, a drug in current use, he said.
Miltefosine is the first oral drug to cure both visceral and cutaneus leishmaniasis. Despite the drug's efficacy, Tipparaju said, miltefosine is limited by its persistence in the bloodstream and long-term side effects. It is also not effective when given to patients co-infected with HIV.
The UIC researchers are attempting to develop an antiparasitic agent that is less toxic than miltefosine and that can kill the parasite inside blood cells. In addition, the researchers are investigating the mechanism of action of the new candidate compounds through a collaboration with Manlio Tolomeo of the Center for Parasitic Diseases in Palermo, Italy. Mechanistic studies could lead to further improvement of promising agents, Tipparaju said.
Sam Hostettler | EurekAlert!
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
New antibody analysis accelerates rational vaccine design
09.08.2018 | Scripps Research Institute
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
15.08.2018 | Physics and Astronomy
15.08.2018 | Earth Sciences
15.08.2018 | Physics and Astronomy