TY - JOUR
T1 - Ferroquine-derived polyamines that target resistant Plasmodium falciparum
AU - Stringer, Tameryn
AU - Wiesner, Lubbe
AU - Smith, Gregory S.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Rising resistance to conventional therapies for malaria has led to the search for novel drugs and strategies with distinct mechanisms of action that may overcome this. Ferroquine is currently the gold standard as far as antimalarial metal-based drugs are concerned and is currently in phase IIb clinical trials as part of the MMV pipeline (in partnership with Sanofi) of antimalarials. It is assumed to inhibit haemozoin formation like chloroquine and maintain its activity in the resistant strain. Here we report two ferroquine-derived polyamines that target a resistant strain of Plasmodium falciparum. Furthermore, upon treatment of Plasmodium falciparum with a ferroquine-derived polyamine, cellular haem fractionation experiments reveal that the inhibition of haemozoin formation is likely not the mechanism responsible for their activity, an important result to aid further clinical development.
AB - Rising resistance to conventional therapies for malaria has led to the search for novel drugs and strategies with distinct mechanisms of action that may overcome this. Ferroquine is currently the gold standard as far as antimalarial metal-based drugs are concerned and is currently in phase IIb clinical trials as part of the MMV pipeline (in partnership with Sanofi) of antimalarials. It is assumed to inhibit haemozoin formation like chloroquine and maintain its activity in the resistant strain. Here we report two ferroquine-derived polyamines that target a resistant strain of Plasmodium falciparum. Furthermore, upon treatment of Plasmodium falciparum with a ferroquine-derived polyamine, cellular haem fractionation experiments reveal that the inhibition of haemozoin formation is likely not the mechanism responsible for their activity, an important result to aid further clinical development.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85067593881&partnerID=MN8TOARS
U2 - 10.1016/j.ejmech.2019.06.023
DO - 10.1016/j.ejmech.2019.06.023
M3 - Article
VL - 179
SP - 78
EP - 83
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -
