Document Detail

Green tea catechins potentiate triclosan binding to enoyl-ACP reductase from Plasmodium falciparum (PfENR).
MedLine Citation:
PMID:  17263522     Owner:  NLM     Status:  MEDLINE    
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.
Shailendra Kumar Sharma; Prasanna Parasuraman; Gyanendra Kumar; Namita Surolia; Avadhesha Surolia
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-31
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  50     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-15     Completed Date:  2007-03-27     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  765-75     Citation Subset:  IM    
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India, National Institute of Immunology, New Delhi 110067, India.
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MeSH Terms
Antimalarials / chemistry*
Catechin / analogs & derivatives,  chemistry*
Chalcones / chemistry
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*,  chemistry*
Escherichia coli / enzymology
Models, Molecular
Plasmodium falciparum / enzymology*
Protein Binding
Quercetin / chemistry
Tea / chemistry*
Triclosan / chemistry*
Reg. No./Substance:
0/Antimalarials; 0/Chalcones; 0/Tea; 117-39-5/Quercetin; 154-23-4/Catechin; 1617-55-6/gallocatechol; 3380-34-5/Triclosan; 487-52-5/butein; 863-03-6/epicatechin gallate; 989-51-5/epigallocatechin gallate; EC Reductase (NADH)

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