Anti malarial models

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 .