Thursday, August 05, 2010

Synthesis and evaluation of oryzalin analogs against Toxoplasma

Bioorg Med Chem Lett. 2010 Jul 8. [Epub ahead of print]

Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii

Endeshaw MM, Li C, Leon JD, Yao N, Latibeaudiere K, Premalatha K, Morrissette N, Werbovetz KA.

Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210-1291, USA.

The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasmagondii 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 36nM 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. AgentsChemother. 2010, 54, 1453], an antimitotic structure-activity relationship for dinitroanilines versus Toxoplasma is presented. Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 20675138 [PubMed - as supplied by publisher]

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