Targeting the fatty acid biosynthesis enzyme, beta-ketoacyl-acyl carrier protein synthase III (PfKASIII), in the identification of novel antimalarial agents.
Targeting the fatty acid biosynthesis enzyme, beta-ketoacyl-acyl carrier protein synthase III (PfKASIII), in the identification of novel antimalarial agents.
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DOI：
10.1021/jm8008103
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发表时间：
2009-02-26
影响因子：
7.3
通讯作者：
Waters NC
中科院分区：
文献类型：
--
作者：
Lee PJ;Bhonsle JB;Gaona HW;Huddler DP;Heady TN;Kreishman-Deitrick M;Bhattacharjee A;McCalmont WF;Gerena L;Lopez-Sanchez M;Roncal NE;Hudson TH;Johnson JD;Prigge ST;Waters NC
The importance of fatty acids to the human malaria parasite, Plasmodium falciparum, and differences due to a type I fatty acid synthesis (FAS) pathway in the parasite, make it an attractive drug target. In the present study, we developed and a utilized a pharmacophore to select compounds for testing against PfKASIII, the initiating enzyme of FAS. This effort identified several PfKASIII inhibitors that grouped into various chemical classes of sulfides, sulfonamides, and sulfonyls. Approximately 60% of the submicromolar inhibitors of PfKASIII inhibited in vitro growth of the malaria parasite. These compounds inhibited both drug sensitive and resistant parasites and testing against a mammalian cell line revealed an encouraging in vitro therapeutic index for the most active compounds. Docking studies into the active site of PfKASIII suggest a potential binding mode that exploits amino acid residues at the mouth of the substrate tunnel.
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影响因子：
56.9
作者：
CONNOLLY, ML
通讯作者：
CONNOLLY, ML
影响因子：
16.2
作者：
CORY, AH;OWEN, TC;CORY, JG
通讯作者：
CORY, JG
DOI：
10.1006/bbrc.2001.6061
发表时间：
2001-12-14
影响因子：
3.1
作者：
Kapoor, M;Dar, MJ;Surolia, N
通讯作者：
Surolia, N
影响因子：
4.9
作者：
He, X;Reynolds, KA
通讯作者：
Reynolds, KA
影响因子：
3.6
作者：
Foth, BJ;Stimmler, LM;McFadden, GI
通讯作者：
McFadden, GI