U.S. flagAn official website of the United States government
                    Here's how you know **Official websites use .gov**
                            
                            A **.gov** website belongs to an official government organization in the United States.
 **Secure .gov websites use HTTPS**
                            
                            A **lock** (                            
                              A locked padlock                                                      
                            
                            ) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.


Menu Agricultural Research Service
						
                    U.S. DEPARTMENT OF AGRICULTURE
 close



Research
                Research Home
                            National Programs
                            Research Projects
                            Scientific Manuscripts
                            International Engagement
                            Scientific Software/Models
                            Databases and Datasets
                            Office of Scientific Quality Review
            Media
                News & Features
                            Multimedia
                            Briefing Room
                            Down on the Farm
                            Press Room
                            Science in Your Shopping Cart
                            Scientific Discoveries
                            Tellus
                            Under the Microscope
            About ARS
                About ARS Home
                            Staff Directory
                            Labs and Research Centers (Map)
                            Headquarter Offices
                            Organizational Chart
                            Employee Services (REE Employees Only)
                            Office of Outreach, Diversity, and Equal Opportunity
            Work With Us
                Work With Us Home
                            ARS Vacancies at USAJOBS
                            Careers at ARS Information
                            Scientific Collaborations
                            Extramural Agreements
                            1890 Faculty Research Sabbatical ProgramSearch small
                    Search
            
            ARS Home
                                About ARS
                                Contact Us




ARS Home Research Publications at this Location





- ARS National Programs
- Search for a scientific manuscript
- Search for a research project
- ARS Software
- Programs and Projects
- Collaborations
- Subjects of Investigation
- Publications

Title:   Author  item
                                            MUI, ERNEST - U CHICAGO, CHICAGO ILitem
                                            SCHIEHSER, GUY - PRINCETON NJitem
                                            MILHOUS, WILBUR - WALTER REED MDitem
                                            HSU, HONGHUE - PRINCETON NJitem
                                            ROBERTS, CRAIG - SCOTLAND UKitem
                                            KIRISITS, MICHAEL - U CHICAGO, CHICAGO ILitem
                                            MUENCH, STEPHEN - ENGLAND UKitem
                                            RICE, DAVID - ENGLAND UKitem
                                            Dubey, Jitenderitem
                                            FOWBLE, JOSEPH - U WASHINGTON, SEATTLEitem
                                            RATHOD, PRADIPSINH - U WASHINGTON, SEATTLEitem
                                            QUEENER, SHERRY - INDIANAPOLIS INitem
                                            LIU, SUSAN - PRINCETON NJitem
                                            JACOBUS, DAVID - PRINCETON NJitem
                                            MCLEOD, RIMA - CHICAGO IL
  Submitted to: PLOS Neglected Tropical Diseases
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 12/7/2007
                                    Publication  Date: 3/1/2008
                                    Citation: Mui, E.J., Schiehser, G.A., Milhous, W.K., Hsu, H., Roberts, C.W., Kirisits, M., Muench, S., Rice, D., Dubey, J.P., Fowble, J.W., Rathod, P.K., Queener, S.F., Liu, S.R., Jacobus, D.P., Mcleod, R. 2008. Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo. PLOS Neglected Tropical Diseases. 2(3):e190.Interpretive Summary: Toxoplasma gondii is a single-celled parasite of all warm-blooded hosts worldwide. It causes mental retardation and loss of vision in children, and abortion in livestock. Cats are the main reservoir of T. gondii because they are the only hosts that can excrete the resistant stage (oocyst) of the parasite in the feces. Humans become infected by eating undercooked meat from infected animals and food and water contaminated with oocysts. Toxoplasmosis causes mortality in many species of animals in the zoos, especially wallabies. Scientists at the Beltsville Agricultural Research Center and  University of Chicago Medical School  report on the finding of a new drug to treat toxoplasmosis. The results will be of interest to biologists, parasitologists, public health workers, and veterinarians
                                Technical Abstract: JPC-2067-B is the primary metabolite of the orally active biguanide JPC-2056 (1-(3-(2-chloro-4-trifluoromethoxyphenyloxypropyl) oxy- (5-isopropyl) biguanide, which is being advanced to clinical trials for malaria.  Efficacy of the prodrug JPC-2056 and the active metabolite JPC-2067-B against T. gondii and T. gondii DHFR as well as toxicity toward mammalian cells were tested.  Herein, we found that JPC-2067-B is highly effective against T. gondii.  We demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM), inhibits the purified enzyme (IC50 6.5 nM), is more efficacious than pyrimethamine, and is cidal in vitro.  JPC-2067-B administered parenterally and the orally administered pro-drug are also effective against T. gondii tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC-2067-B was developed.  We  found that the three main parasite clonal types and isolates from South and Central America, the U.S., Canada, China and Sri Lanka have the same amino acid sequences preserving  key binding sites for the triazine.  JPC-2067-B and JPC-2056 have potential to be more effective and possibly less toxic treatments for toxoplasmosis than currently available medicines.


Return to top


Connect with ARS Sign up


ARS Home
                            USDA.gov
                            Plain Writing
                            Policies & Links
                            Civil Rights Statements
                            FOIA
                            Accessibility Statement
                            Privacy Policy
                            Non-Discrimination Statement
                            Quality of Information
                            USA.gov
                            WhiteHouse.gov