 |
PDBsum entry 4r6t
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
4r6t
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Two-Pronged attack: dual inhibition of plasmodium falciparum m1 and m17 metalloaminopeptidases by a novel series of hydroxamic acid-Based inhibitors.
|
|
|
Authors
|
|
S.N.Mistry,
N.Drinkwater,
C.Ruggeri,
K.K.Sivaraman,
S.Loganathan,
S.Fletcher,
M.Drag,
A.Paiardini,
V.M.Avery,
P.J.Scammells,
S.Mcgowan.
|
|
|
Ref.
|
|
J Med Chem, 2014,
57,
9168-9183.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Plasmodium parasites, the causative agents of malaria, have developed resistance
to most of our current antimalarial therapies, including artemisinin combination
therapies which are widely described as our last line of defense. Antimalarial
agents with a novel mode of action are urgently required. Two Plasmodium
falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the
erythrocytic stage of infection and have been validated as potential
antimalarial targets. Using compound-bound crystal structures of both enzymes,
we have used a structure-guided approach to develop a novel series of inhibitors
capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite
growth in culture. Herein we describe the design, synthesis, and evaluation of a
series of hydroxamic acid-based inhibitors and demonstrate the compounds to be
exciting new leads for the development of novel antimalarial therapeutics.
|
|
|
|
|
|
|
