@article{2742a1f8a7a94360a22559dee9711b6a,
title = "Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents",
abstract = "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%).",
keywords = "Schistosomiasis, X-ray crystallographic studies, aminopiperidine, aminopyrrolidine, oxamniquine, structure-activity relationships",
author = "Anastasia Rugel and Tarpley, {Reid S.} and Ambrosio Lopez and Travis Menard and Guzman, {Meghan A.} and Taylor, {Alexander B.} and Xiaohang Cao and Dmytro Kovalskyy and Chevalier, {Fr{\'e}d{\'e}ric D.} and Anderson, {Timothy J.C.} and Hart, {P. John} and Loverde, {Philip T.} and McHardy, {Stanton F.}",
note = "Funding Information: The research was supported by a grant to P.T.L. and P.J.H. from the NIH, NIAID R01 AI115691. P.J.H. (AQ-1399) was funded by The Welch Foundation. The X-ray Crystallography Core Laboratory is a part of the Institutional Research Cores at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) supported by the Office of the Vice President for Research and the Mays Cancer Center (NIH P30 CA054174). This work is based upon research conducted at the Northeastern Collaborative Access Team beamlines, which are funded by the National Institute of General Medical Sciences from the National Institutes of Health (P41 GM103403). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2018",
month = oct,
day = "11",
doi = "10.1021/acsmedchemlett.8b00257",
language = "English (US)",
volume = "9",
pages = "967--973",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",
number = "10",
}