ERRA TA In the article entitled "The Net Hydration of Deoxyribonucleic Acid," by K. Lemone Yielding and Gordon M. Tomkins, which appeared on pages 983-989 of this volume (July issue), the second sentence of the caption to Figure 4 (page 987) should read: "Reaction mixture for both cells contained 0.05 M tris pH 8.0, EDTA 5 X 10-4 M, crystalline beef liver glutamic dehydrogenase 5 mg/ml, propylene glycol 2%, diethylstibestrol 2 X 10-4 M, and, in the upper diagram, L-leucine 2.4 X 10-2 M."
Trypanosoma brucei E164 and a dyskinetoplastic derivative, Dysk164, were injected into mice that were treated subsequently with methylglyoxal-bis-guanylhydrazone, berenil, ethidium bromide, and acriflavine. Additionally, parasites were photoaffinity labeled with ethidium monoazide to effect covalent drug attachment prior to injection into animals. In all cases, killing of animals with E164 was blocked by the drug treatment, whereas killing due to Dysk164 was not. These findings are consistent with the view that the intact kinetoplast plays an essential role in the action of these drugs.
Twelve 4-urea-5,7-dichlorokynurenic acid derivatives were synthesized by reacting the 4-tosylimino derivative of 5,7-dichlorokynurenate methyl ester first with triphosgene and then with a secondary amine. Compounds were screened in mice for anticonvulsant activity using maximal electroshock (MES), subcutaneous pentylenetetrazole (Met), and threshold tonic extension (TTE) tests. A rotorod test was used to determine neurotoxicity. Seven of the derivatives had anticonvulsant activity in TTE testing at 100 mg/kg. One compound, 2-methyl carboxylate-5,7-dichloro-4-([¿diphenylamino¿-carbonyl]amino)-quino line, had an ED50 value of 134 mg/kg (95% conf. int.: low-78.5, high-205.7; slope 1.9, SE = 0.44) in TTE testing. Two derivatives had MES activity. Only one compound, an N,N-diethylamino derivative, was neurotoxic in the rotorod test. Compounds were screened at a 10-microM concentration for activity in displacing 5,7-dichlorokynurenic acid from synaptosomal membrane fragments. Since 9 of the 12 compounds synthesized and tested have demonstrated anticonvulsant activity, this class of chemicals offers promise for the production of useful therapeutic agents.
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