Design, Development, Synthesis, and Docking Analysis of 2-substituted Triclosan Analogs as Inhibitors for Plasmodium falciparum Enoyl-ACP Reductase

Kapoor, Neha and Banerjee, Tanushree and Babu, Ponnusamy and Maity, Koustav and Surolia, Namita and Surolia, Avadhesha (2009) Design, Development, Synthesis, and Docking Analysis of 2-substituted Triclosan Analogs as Inhibitors for Plasmodium falciparum Enoyl-ACP Reductase. In: Iubmb life, 61 (11). pp. 1083-1091.

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Abstract

A structure-based approach has been adopted to develop 2'substituted analogs of triclosan. The Cl at position 2' in ring B of triclosan was chemically substituted with other functional groups like NH2, NO2 and their inhibitory potencies against PfENR were determined. The binding energies of the 2' substituted analogs of triclosan for enoyl-acyl carrier protein reductase (ENR) of Plasmodium falciparum were determined using Autodock. Based on the autodock results, we synthesized the potential compounds. The IC50 and inhibition constant (K-i) of 2' substituted analogs of triclosan were determined against purified PfENR. Among them, two compounds,2-(2'-Amino-4'-chloro-phenoxy)-5-chloro-phenol (compound 4) and 5-chloro-2-(4'-chloro-2'-nitro-phenoxy)-phenol) (compound 5) exhibited good potencies. Compound 4 followed uncompetitive inhibition kinetics with crotonoyl CoA and competitive with NADH. It was shown to have an IC50 of 110 nM; inhibition constant was 104 nM with the substrate and 61 nM with the cofactor. IC50 Of compound 5 was determined to be 229 nM. Compounds 4 and 5 showed significant inhibition of the parasite growth in P. falciparum culture. (C) 2009 IUBMB IUBMB Life, 61(11):1083-1091, 2009.

Item Type:	Journal Article
Publication:	Iubmb life
Publisher:	JOHN WILEY & SONS INC
Additional Information:	copyright of this article belongs to JOHN WILEY & SONS INC.
Keywords:	Triclosan; Triclosan analogs; Plasmodium falciparum; Enoyl-ACP reductase.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	05 Jan 2010 06:06
Last Modified:	19 Sep 2010 05:53
URI:	http://eprints.iisc.ac.in/id/eprint/25158

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