Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents
| Autor: | Anastasia Rugel, Reid S. Tarpley, Ambrosio Lopez, Travis Menard, Meghan A. Guzman, Alexander B. Taylor, Xiaohang Cao, Dmytro Kovalskyy, Frédéric D. Chevalier, Timothy J. C. Anderson, P. John Hart, Philip T. LoVerde, Stanton F. McHardy |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug media_common.quotation_subject Schistosomiasis Drug resistance 01 natural sciences Biochemistry 03 medical and health sciences parasitic diseases Drug Discovery medicine media_common biology 010405 organic chemistry Organic Chemistry biology.organism_classification medicine.disease Small molecule Virology 0104 chemical sciences Oxamniquine Praziquantel 030104 developmental biology Parasitic disease Schistosoma mansoni medicine.drug |
| Zdroj: | ACS Medicinal Chemistry Letters. 9:967-973 |
| ISSN: | 1948-5875 |
| DOI: | 10.1021/acsmedchemlett.8b00257 |
| Popis: | [Image: see text] Schistosomiasis is a major human parasitic disease afflicting more than 250 million people, historically treated with chemotherapies praziquantel or oxamniquine. Since oxamniquine is species-specific, killing Schistosoma mansoni but not other schistosome species (S. haematobium or S. japonicum) and evidence for drug resistant strains is growing, research efforts have focused on identifying novel approaches. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust structure–activity relationship (SAR) program that identified several new lead compounds with effective worm killing. These studies culminated in the discovery of compound 12a, which demonstrated broad-species activity in killing S. mansoni (75%), S. haematobium (40%), and S. japonicum (83%). |
| Databáze: | OpenAIRE |
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