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 (k₅) of the reversible and loose PfENR-EGCG binary complex to a tight [PfENR-EGCG]^∗ or EI^∗ complex was calculated to be 4.0 × 10⁻² s⁻¹. The low dissociation rate constant (k₆) 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 k₆ 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.