Epigallocatechin gallate is a slow-tight binding inhibitor of enoyl-ACP reductase from Plasmodium falciparum.

Epigallocatechin gallate (EGCG) is known to have numerous pharmacological properties. In the present study, we have shown that EGCG inhibits enoyl-acyl carrier protein reductase of Plasmodium falciparum (PfENR) by following a two-step, slow, tight-binding inhibition mechanism. The association/isomerization rate constant (k(5)) of the reversible and loose PfENR-EGCG binary complex to a tight PfENR-EGCG or EI() complex was calculated to be 4.0x10(-2) s(-1). The low dissociation rate constant (k(6)) of the PfENR-EGCG complex confirms the tight-binding nature of EGCG. EGCG inhibited PfENR with the overall inhibition constant (K(i)()) of 7.0+/-0.8 nM. Further, we also studied the effect of triclosan on the inhibitory activity of EGCG. Triclosan lowered the k(6) of the EI() complex by 100 times, lowering the overall K(i)() of EGCG to 97.5+/-12.5 pM. The results support EGCG as a promising candidate for the development of tea catechin based antimalarial drugs.