1240613-28-8Relevant articles and documents
Identification and development of novel inhibitors of toxoplasma gondii enoyl reductase
Tipparaju, Suresh K.,Muench, Stephen P.,Mui, Ernest J.,Ruzheinikov, Sergey N.,Lu, Jeffrey Z.,Hutson, Samuel L.,Kirisits, Michael J.,Prigge, Sean T.,Roberts, Craig W.,Henriquez, Fiona L.,Kozikowski, Alan P.,Rice, David W.,McLeod, Rima L.
experimental part, p. 6287 - 6300 (2010/12/25)
Toxoplasmosis causes significant morbidity and mortality, and yet available medicines are limited by toxicities and hypersensitivity. Because improved medicines are needed urgently, rational approaches were used to identify novel lead compounds effective against Toxoplasma gondii enoyl reductase (TgENR), a type II fatty acid synthase enzyme essential in parasites but not present in animals. Fifty-three compounds, including three classes that inhibit ENRs, were tested. Six compounds have antiparasite MIC90s ≤ 6 μM without toxicity to host cells, three compounds have IC90s A?. The crystal structure reveals that the aliphatic side chain of compound 19 occupies, as predicted, space made available by replacement of a bulky hydrophobic residue in homologous bacterial ENRs by Ala in TgENR. This provides a paradigm, conceptual foundation, reagents, and lead compounds for future rational development and discovery of improved inhibitors of T. gondii.
