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.