Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2′-Substituted triclosan derivatives

Joel S. Freundlich; Min Yu; Edinson Lucumi; MacK Kuo; Han Chun Tsai; Juan Carlos Valderramos; Luchezar Karagyozov; William R. Jacobs; Guy A. Schiehser; David A. Fidock; David P. Jacobus; James C. Sacchettini

doi:10.1016/j.bmcl.2006.01.051

Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2′-Substituted triclosan derivatives

Joel S. Freundlich, Min Yu, Edinson Lucumi, MacK Kuo, Han Chun Tsai, Juan Carlos Valderramos, Luchezar Karagyozov, William R. Jacobs, Guy A. Schiehser, David A. Fidock, David P. Jacobus, James C. Sacchettini

Microbiology & Immunology

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59 Scopus citations

Abstract

2′-Substituted analogs of triclosan have been synthesized to target inhibition of the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of these compounds exhibit good potency (EC ₅₀ < 500 nM) against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and modest (IC₅₀ = 1-20 μM) potency against purified PfENR enzyme. Compared to triclosan, this survey of 2′-substituted derivatives has afforded gains in excess of 20- and 30-fold versus the 3D7 and Dd2 strains of parasite, respectively.

Original language	English (US)
Pages (from-to)	2163-2169
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2006.01.051
State	Published - Apr 15 2006

Keywords

Antimalarial
Diaryl ether
Phenol

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2006.01.051

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Freundlich, J. S., Yu, M., Lucumi, E., Kuo, M., Tsai, H. C., Valderramos, J. C., Karagyozov, L., Jacobs, W. R., Schiehser, G. A., Fidock, D. A., Jacobus, D. P., & Sacchettini, J. C. (2006). Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2′-Substituted triclosan derivatives. Bioorganic and Medicinal Chemistry Letters, 16(8), 2163-2169. https://doi.org/10.1016/j.bmcl.2006.01.051

Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2′-Substituted triclosan derivatives. / Freundlich, Joel S.; Yu, Min; Lucumi, Edinson et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 8, 15.04.2006, p. 2163-2169.

Research output: Contribution to journal › Article › peer-review

Freundlich, JS, Yu, M, Lucumi, E, Kuo, M, Tsai, HC, Valderramos, JC, Karagyozov, L, Jacobs, WR, Schiehser, GA, Fidock, DA, Jacobus, DP & Sacchettini, JC 2006, 'Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2′-Substituted triclosan derivatives', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 8, pp. 2163-2169. https://doi.org/10.1016/j.bmcl.2006.01.051

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abstract = "2′-Substituted analogs of triclosan have been synthesized to target inhibition of the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of these compounds exhibit good potency (EC 50 < 500 nM) against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and modest (IC50 = 1-20 μM) potency against purified PfENR enzyme. Compared to triclosan, this survey of 2′-substituted derivatives has afforded gains in excess of 20- and 30-fold versus the 3D7 and Dd2 strains of parasite, respectively.",

keywords = "Antimalarial, Diaryl ether, Phenol",

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doi = "10.1016/j.bmcl.2006.01.051",

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AU - Tsai, Han Chun

AU - Valderramos, Juan Carlos

AU - Karagyozov, Luchezar

AU - Jacobs, William R.

AU - Schiehser, Guy A.

AU - Fidock, David A.

AU - Jacobus, David P.

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AB - 2′-Substituted analogs of triclosan have been synthesized to target inhibition of the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of these compounds exhibit good potency (EC 50 < 500 nM) against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and modest (IC50 = 1-20 μM) potency against purified PfENR enzyme. Compared to triclosan, this survey of 2′-substituted derivatives has afforded gains in excess of 20- and 30-fold versus the 3D7 and Dd2 strains of parasite, respectively.

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Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2′-Substituted triclosan derivatives

Abstract

Keywords

ASJC Scopus subject areas

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