Sexual development of malaria parasites is inhibited in vitro by the neem extract azadirachtin, and its semi-synthetic analogues.
We have shown that azadirachtin, a compound from the neem tree, Azadirachta indica, and selected semi-synthetic derivatives, block the development of the motile male malarial gamete in vitro. Changes in the hemiacetal group at position C11 in the molecule result in a loss of activity in this assay. The motility of fully formed male gametes, and other selected flagellated cells, is unaffected by azadirachtin in vitro. These findings raise the possibility of developing azadirachtin-based compounds as antimalarials with transmission-blocking potential, as well as permitting the further study of structure-activity relationships in these compounds.
Jones
I W
IW
Department of Biology, Imperial College of Science, Technology and Medicine, London, UK.
Denholm
A A
AA
Ley
S V
SV
Lovell
H
H
Wood
A
A
Sinden
R E
RE
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D005407:Flagella / Q000187:drug effects; D006801:Humans; D036701:Limonins; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D036701:Limonins; D014315:Triterpenes; C010329:azadirachtin