Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2'-substituted triclosan derivatives. Academic Article

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 (EC50<500 nM) against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and modest (IC50=1-20 microM) 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.

authors

• Sacchettini, James

published proceedings

• Bioorg Med Chem Lett

altmetric score

• 3

author list (cited authors)

• Freundlich, J. S., Yu, M., Lucumi, E., Kuo, M., Tsai, H., Valderramos, J., ... Sacchettini, J. C.

citation count

• 44

complete list of authors

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

publication date

• April 2006

publisher

• Elsevier  Publisher

published in

• Bioorganic and Medicinal Chemistry Letters  Journal

keywords

• Animals
• Antimalarials
• Crystallography, X-Ray
• Drug Resistance, Microbial
• Enoyl-(acyl-carrier-protein) Reductase (nadh)
• Ethers
• Plasmodium Falciparum
• Structure-Activity Relationship
• Triclosan

PubMed Central ID

• 16466916

Digital Object Identifier (DOI)

• 10.1016/j.bmcl.2006.01.051

start page

• 2163

end page

• 2169

volume

• 16

issue

• 8

URL

• http://dx.doi.org/10.1016/j.bmcl.2006.01.051