Purine and pyrimidine pathways as targets in plasmodium falciparum

María Belén Cassera, Yong Zhang, Keith Z. Hazleton, Vern L. Schramm

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Malaria is a leading cause of morbidity and mortality in the tropics. Chemotherapeutic and vector control strategies have been applied for more than a century but have not been efficient in disease eradication. Increased resistance of malaria parasites to drug treatment and of mosquito vectors to insecticides requires the development of novel chemotherapeutic agents. Malaria parasites exhibit rapid nucleic acid synthesis during their intraerythrocytic growth phase. Plasmodium purine and pyrimidine metabolic pathways are distinct from those of their human hosts. Thus, targeting purine and pyrimidine metabolic pathways provides a promising route for novel drug development. Recent developments in enzymatic transition state analysis have provided an improved route to inhibitor design targeted to specific enzymes, including those of purine and pyrimidine metabolism. Modern transition state analogue drug discovery has resulted in transition state analogues capable of binding to target enzymes with unprecedented affinity and specificity. These agents can provide specific blocks in essential pathways. The combination of tight binding with the high specificity of these logically designed inhibitors, results in low toxicity and minor side effects. These features reduce two of the major problems with the current antimalarials. Transition state analogue design is being applied to generate new lead compounds to treat malaria by targeting purine and pyrimidine pathways.

Original languageEnglish (US)
Pages (from-to)2103-2115
Number of pages13
JournalCurrent topics in medicinal chemistry
Volume11
Issue number16
DOIs
StatePublished - Aug 1 2011

Keywords

  • Antimalarials
  • Immucillins
  • Malaria
  • Purines
  • Pyrimidines
  • Transition state analogues

ASJC Scopus subject areas

  • Drug Discovery

Fingerprint Dive into the research topics of 'Purine and pyrimidine pathways as targets in plasmodium falciparum'. Together they form a unique fingerprint.

  • Cite this