title: Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii.
abstract: 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.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210-1291, USA.
authors.forename: Molla M
authors.initials: MM
authors.lastname: Endeshaw
authors.forename: Catherine
authors.initials: C
authors.lastname: Li
authors.forename: Jessica
authors.initials: J
authors.lastname: de Leon
authors.forename: Ni
authors.initials: N
authors.lastname: Yao
authors.forename: Kirk
authors.initials: K
authors.lastname: Latibeaudiere
authors.forename: Kokku
authors.initials: K
authors.lastname: Premalatha
authors.forename: Naomi
authors.initials: N
authors.lastname: Morrissette
authors.forename: Karl A
authors.initials: KA
authors.lastname: Werbovetz
mesh_terms: D000818:Animals; D004136:Dinitrobenzenes / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000469:parasitology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D013424:Sulfanilamides / Q000737:chemistry / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D004136:Dinitrobenzenes; D013424:Sulfanilamides; C012465:oryzalin