Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Endeshaw, Molla M.¹  Li, Catherine²  de Leon, Jessica²  Yao, Ni²  Latibeaudiere, Kirk¹  Premalatha, Kokku¹  Morrissette, Naomi²  Werbovetz, Karl A.¹ 

[1] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA

[2] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

关键词: Toxoplasma;    Tubulin;    Oryzalin;    Trifluralin;    Dinitroaniline;   

DOI  :  10.1016/j.bmcl.2010.07.003

来源: Elsevier

【 摘 要 】

The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasma gondii is reported. Using in vitro cultures of parasites in human fibroblasts, we determined that most of these compounds selectively disrupted Toxoplasma microtubules, and several displayed sub-micromolar potency against the parasite. The most potent compound was N(1),N(1)-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3-benzenediamine (18b), which displayed an IC(50) value of 36 nM against intracellular T. gondii. Based on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li, C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. Agents Chemother. 2010, 54, 1453], an antimitotic structure-activity relationship for dinitroanilines versus Toxoplasma is presented. (C) 2010 Elsevier Ltd. All rights reserved.

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