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Two novel approaches for treating malaria have been reported recently. A
novel alkaloid called tazopsine, isolated from a plant in Madagascar, is
found to be effective against the early liver stages of the malaria parasite
and holds promise as a causal prophylactic against development of malaria
parasites in the human body. On the other, erythrocyte guanine nucleotide
regulatory protein Gs has been investigated as a novel antimalarial target
with a commonly used antihypertensive propranalol found to be effective in
reducing its activity.
French researchers have isolated a novel morphinan alkaloid, tazopsine, from a plant, Strychnopsis thouarsii, traditionally used against malaria in Madagascar. This compound and readily
obtained semisynthetic derivatives were tested for inhibitory activity against
liver stage development in vitro (P. falciparum and P. yoelii)
and in vivo (P. yoelii). Tazopsine fully inhibited the development of
P. yoelii and P. falciparum hepatic parasites in cultured primary hepatocytes,
with inhibition being most pronounced during the early developmental stages. Oral administration of N-cyclopentyl-tazopsine
(NCP-tazopsine), a derivative with similar inhibitory activity but with lower
toxicity, completely protected mice
from a sporozoite challenge. Thus tazopsine has been shown to be specifically active against the liver stage,
but inactive against the blood forms of the malaria parasite. This unique
specificity in an antimalarial drug severely restricts the pressure for the
selection of drug resistance to a parasite stage limited both in numbers and
duration, thus allowing researchers to envisage the incorporation of a true
causal prophylactic in malaria control programs.
More:
Carraz M, Jossang A, Franetich JF, Siau A, Ciceron L, et al. (2006) A
Plant-Derived Morphinan as a Novel Lead Compound Active against Malaria Liver
Stages . PLoS Med 3(12): e513 Avilable at
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030513
Kasturi Haldar and colleagues from Northwestern University
Medical School, Chicago, investigated a protein in red blood cells called the erythrocyte
guanine nucleotide regulatory protein Gs, as a novel antimalarial target. They
found that propranolol, a commonly used antihypertensive drug, decreased Gs activity in red blood cells and inhibited
blood-stage malarial parasite growth.
When used in combination with existing antimalarials in cell culture,
propranolol reduced the dose of existing antimalarial drugs required to treat
animal models of malarial infection. Erythrocyte G may therefore be a novel
antimalarial target; in addition, drugs antagonising erythrocyte Gs could be
used in combination therapies with existing antimalarial drugs.
More:
Murphy SC, Harrison T, Hamm HE, Lomasney JW, Mohandas N, et al.
(2006) Erythrocyte G protein as a novel target for malarial chemotherapy. PLoS
Med 3(12): e528. Available at
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030528
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