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EVALUATION OF NEWER
ANTIMALARIALS
Dr Pruthvi D
Final Year PG
MD Pharmacology
History
Life cycle
Drug development strategy
New drugs in pipeline
Malaria vaccine
HISTORY
LIFE CYCLE
2 weeks
Symptoms
DRUG DEVELOPMENT STRATEGY
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
TARGET BASED SCREENS
P21
8
TRANSMISSION ASSAY
Direct feeding assay
Membrane feeding assay
RADICAL CURE ASSAY
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
NEW DRUGS IN PIPELINE
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
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 .