Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii

✍ Scribed by Molla M. Endeshaw; Catherine Li; Jessica de Leon; Ni Yao; Kirk Latibeaudiere; Kokku Premalatha; Naomi Morrissette; Karl A. Werbovetz

• Book ID: 104004623
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 764 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.07.003

✦ Synopsis

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.