title: Dihydrofolate reductase inhibitors: developments in antiparasitic chemotherapy.
abstract: BACKGROUND
  Infections caused by parasitic protozoa present a growing health concern, particularly in developing parts of the world. Although malaria is clearly the most well-known and deadly of these diseases, infections caused by other parasites, such as Toxoplasma, Cryptosporidia and Trypanosoma are emerging infectious threats. The success of inhibitors of the enzyme dihydrofolate reductase (DHFR) against malaria has encouraged further exploration of this strategy against other parasites.
  
  
  OBJECTIVE
  This review presents antifolate inhibitors that have appeared in the patent literature and elaborates on their potency and selectivity against the DHFR enzyme from parasitic protozoa.
  
  
  METHODS
  The patent literature since 1994 was surveyed for antiparasitic DHFR inhibitors.
  
  
  CONCLUSIONS
  Over the past several years, there have been a variety of novel, potent and selective inhibitors disclosed in patents, primarily from academic researchers. This review summarizes the recent development of antifolates as specific agents against parasitic protozoa.
authors.affiliation: University of Connecticut, Department of Pharmaceutical Sciences, 69 N Eagleville Road, Storrs, CT 06269, USA +1 860 486 6145 ; +1 860 486 6857 ; amy.anderson@uconn.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Bolstad
authors.forename: Erin Sd
authors.initials: ES
authors.lastname: Bolstad
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Wright
authors.forename: Amy C
authors.initials: AC
authors.lastname: Anderson