Anti malarial models

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  1. 1. EVALUATION OF NEWER ANTIMALARIALS Dr Pruthvi D Final Year PG MD Pharmacology
  2. 2. History Life cycle Drug development strategy New drugs in pipeline Malaria vaccine
  3. 3. HISTORY
  4. 4. LIFE CYCLE 2 weeks Symptoms
  5. 5. DRUG DEVELOPMENT STRATEGY
  6. 6. CELL BASED SCREENS Blood stage screens: Liver stage screens: Transmission screens SYBR YOYO THE SYTO SERIES PRO- PIDIUM IODIDE ACRIDINE ORANGE THE HOECHST DYE SERIES PICOGREEN
  7. 7. TARGET BASED SCREENS P21 8
  8. 8. TRANSMISSION ASSAY Direct feeding assay Membrane feeding assay
  9. 9. RADICAL CURE ASSAY
  10. 10. IC 50 of P falciparum blood stages- parasite proliferation assay P vivax blood stage sensitivity- schizont maturation assay Transmission blocking activity- viability of purified gametocytes or ookinetes Ability of gametocytes to infect mosquitoes- standard membrane feeding assay & direct feeding from infected mice assay
  11. 11. NEW DRUGS IN PIPELINE
  12. 12. MALARIA VACCINE No human vaccine against protozoal diseases. Species specific. Main targets are P falciparum & P vivax. First vaccine is RTS,S Alternative strategies Attenuated P falciparum sporozoits
  13. 13. REFERENCES Review Of Antimalarial Drug Discovery ,Anna Caroline C Aguiar Et Al, Mem Inst Oswaldo Cruz, Rio De Janeiro, Vol. 107(7): 831-845, November 2012 . Antimalarial Drug Discovery Approaches And Progress Towards New Medicines, Erika L. Flannery1, Arnab K. Chatterjee2 And Elizabeth A. Winzeler1 , Nature Reviews , Microbiology ,Volume 11, December 2013 Malaria medicines: a glass half full? , Timothy N. C. Wells1, Rob Hooft van Huijsduijnen1 and Wesley C. Van Voorhis1,2 , Nature Reviews Drug Discovery , May 2015; doi:10.1038/nrd4573 .