Transition-state inhibitors of purine salvage and other prospective enzyme targets in malaria

Rodrigo G. Ducati, Hilda A. Namanja-Magliano, Vern L. Schramm

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Malaria is a leading cause of human death within the tropics. The gradual generation of drug resistance imposes an urgent need for the development of new and selective antimalarial agents. Kinetic isotope effects coupled to computational chemistry have provided the relevant details on geometry and charge of enzymatic transition states to facilitate the design of transition-state analogs. These features have been reproduced into chemically stable mimics through synthetic chemistry, generating inhibitors with dissociation constants in the pico- to femto-molar range. Transition-state analogs are expected to contribute to the control of malaria.

Original languageEnglish (US)
Pages (from-to)1341-1360
Number of pages20
JournalFuture Medicinal Chemistry
Volume5
Issue number11
DOIs
StatePublished - Jul 2013

Fingerprint

Malaria
Antimalarials
Enzymes
Drug Resistance
Isotopes
Cause of Death
purine

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Molecular Medicine

Cite this

Transition-state inhibitors of purine salvage and other prospective enzyme targets in malaria. / Ducati, Rodrigo G.; Namanja-Magliano, Hilda A.; Schramm, Vern L.

In: Future Medicinal Chemistry, Vol. 5, No. 11, 07.2013, p. 1341-1360.

Research output: Contribution to journalArticle

Ducati, Rodrigo G. ; Namanja-Magliano, Hilda A. ; Schramm, Vern L. / Transition-state inhibitors of purine salvage and other prospective enzyme targets in malaria. In: Future Medicinal Chemistry. 2013 ; Vol. 5, No. 11. pp. 1341-1360.
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