Determination of antiplasmodial activity and binding affinity of curcumin and demethoxycurcumin towards PfTrxR.
In our study, the inhibitory activity of curcuminoids towards Plasmodium falciparum thioredoxin reductase (PfTrxR) was determined using LC-MS-based functional assay and showed that only demethoxycurcumin (DMC) inhibited PfTrxR (IC50: 2 μM). In silico molecular modelling was used to ascertain and further confirm that the binding affinities of curcumin and DMC are towards the dimer interface of PfTrxR. The in vitro antiplasmodial activities of curcumin and DMC were evaluated and shown to be active against chloroquine (CQ)-sensitive (D6 clone) and moderately active against CQ-resistant (W2 clone) strains of Plasmodium falciparum while no cytotoxicity was observed against Vero cells.
a Department of Pharmacal Sciences , Harrison School of Pharmacy, Auburn University , 4306B Walker Building, Auburn , 36849 AL , USA.
Ranjith
R
Munigunti
Symon
S
Gathiaka
Orlando
O
Acevedo
Rajnish
R
Sahu
Babu
B
Tekwani
Angela I
AI
Calderón
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D036381:Diarylheptanoids; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*; D014709:Vero Cells
D000962:Antimalarials; D036381:Diarylheptanoids; D013880:Thioredoxin-Disulfide Reductase; D003474:Curcumin; C050229:demethoxycurcumin