Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development
نویسندگان
چکیده
منابع مشابه
Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit Trypanosoma brucei Pteridine Reductase in Support of Early-Stage Drug Discovery
Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated the potential of a previously identified class of thiadiazole inhibitors of Leishmania major PTR1 for activity against Trypanosoma brucei (Tb). We solved crystal structures of several TbPTR1-inhibitor complexes to guide the structure-based design of new thiadiazole derivatives. Subseque...
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Cryptosporidiosis is an emerging infectious disease that can be life-threatening in an immune-compromised individual and causes gastrointestinal distress lasting up to 2 weeks in an immune-competent individual. There are few therapeutics available for effectively treating this disease. We have been exploring dihydrofolate reductase (DHFR) as a potential target in Cryptosporidium. On the basis o...
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This issue of Acta Crystallographica Section F is dedicated towards structural investigations on proteins associated with molecular parasitology, specifically research linked to protozoan pathogens. It is in line with the previous special sections or issues contributed by the RIKEN-UK structural genomics consortium (December 2009), the Joint Center for Structural Genomics in October 2010 (Weiss...
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Pteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-specie...
متن کاملIn Silico Identification and In Vitro Evaluation of Natural Inhibitors of Leishmania major Pteridine Reductase I.
In a continuation of our computational efforts to find new natural inhibitors of a variety of target enzymes from parasites causing neglected tropical diseases (NTDs), we now report on 15 natural products (NPs) that we have identified as inhibitors of Leishmania major pteridine reductase I (LmPTR1) through a combination of in silico and in vitro investigations. Pteridine reductase (PTR1) is an ...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2008
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.0704384105