Sharma, Shailendra Kumar and Parasuraman, Prasanna and Kumar, Gyanendra and Surolia, Namita and Surolia, Avadhesha (2007) Green Tea Catechins Potentiate Triclosan Binding to Enoyl-ACP Reductase from Plasmodium falciparum (PfENR). In: Journal of Medicinal Chemistry, 50 (4). pp. 765-775.
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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 $K_i$ values in the nanomolar range, EGCG being the best with 79 \pm 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:||Journal Article|
|Additional Information:||Copyright of this article belongs to American Chemical Society.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||29 Jul 2008|
|Last Modified:||19 Sep 2010 04:48|
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