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(s)) of the reversible and loose PfENR-EGCG binary complex to a tight [PfENR-EGCG]* or EI* complex was calculated to be 4.0 x 10(-2) S-1. The low dissociation rate constant (k(G)) of the [PfENR-EGCG]* complex confirms the tight-binding nature of EGCG. EGCG inhibited PfENR with the overall inhibition constant (Ki*) 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. (C) 2008 Elsevier Inc. All rights reserved.