Green tea catechins potentiate triclosan binding to enoyl-ACP reductase from Plasmodium falciparum (PfENR)

Sharma, Shailendra Kumar ; Parasuraman, Prasanna ; Kumar, Gyanendra ; Surolia, Namita ; Surolia, Avadhesha (2007) Green tea catechins potentiate triclosan binding to enoyl-ACP reductase from Plasmodium falciparum (PfENR) Journal of Medicinal Chemistry, 50 (4). pp. 765-775. ISSN 0022-2623

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Official URL: http://pubs.acs.org/doi/abs/10.1021/jm061154d

Related URL: http://dx.doi.org/10.1021/jm061154d

Abstract

We have investigated the mechanism of inhibition of enoyl-acyl carrier protein reductase of Plasmodium falciparum (PfENR) by triclosan in the presence of a few important catechins and related plant polyphenols. The examined flavonoids inhibited PfENR reversibly with Ki values in the nanomolar range, EGCG being the best with 79±2.67 nM. The steady-state kinetics revealed time dependent inhibition of PfENR by triclosan, demonstrating that triclosan exhibited slow tight-binding kinetics with PfENR in the presence of these compounds. Additionally, all of them potentiated the binding of triclosan with PfENR by a two-step mechanism resulting in an overall inhibition constant of triclosan in the low picomolar concentration range. The high affinities of tea catechins and the potentiation of binding of triclosan in their presence are readily explained by molecular modeling studies. The enhancement in the potency of triclosan induced by these compounds holds great promise for the development of effective antimalarial therapy.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society.
ID Code:55377
Deposited On:18 Aug 2011 12:09
Last Modified:03 Oct 2011 14:07

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