Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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%).

Original languageEnglish (US)
Pages (from-to)967-973
Number of pages7
JournalACS Medicinal Chemistry Letters
Volume9
Issue number10
DOIs
StatePublished - Oct 11 2018

Keywords

  • Schistosomiasis
  • X-ray crystallographic studies
  • aminopiperidine
  • aminopyrrolidine
  • oxamniquine
  • structure-activity relationships

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents'. Together they form a unique fingerprint.

Cite this