Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Environ Toxicol Pharmacol. 2009 Mar;27(2):271-6. doi: 10.1016/j.etap.2008.11.007. Epub 2008 Nov 24.
The aim of the present study was to evaluate toxicological parameters of following compounds: 1a (4,4'-dichloro-diphenyl diselenide [(ClPhSe)(2)]), 1b (3,3'-ditrifluoromethyl-diphenyl diselenide [(F(3)CPhSe)(2)]) and 1c (4,4'-dimethoxyl-diphenyl diselenide [(CH(3)OPhSe)(2)]). Calculated lethal dose (LD(50)) values for mice exposed, by oral route, to a single application of compounds 1a, 1b or 1c were estimated to be >381, 278 and >372mg/kg, respectively. Compounds 1a and 1b significantly reduced body weight gain as well as food and water intake in mice. δ-Aminolevulinate dehydratase (δ-ALA-D) and catalase activities were inhibited in mice which received the highest dose of compounds 1a or 1b. Exposure to compounds 1a, 1b and 1c did not modify lipid peroxidation, vitamin C levels, cerebral Na(+)/K(+)-ATPase activity and the biochemical parameters evaluated. The important point for medicinal chemistry is that the structural modifications are not introducing toxicity for the compounds in mice.
1a（4,4'-二氯-二苯二硒醚[(ClPhSe)2]）、1b（3,3'-二三氟甲基-二苯二硒醚[(F3CPhSe)2]）和 1c（4,4'-二甲氧基-二苯二硒醚[(CH3OPhSe)2]）。通过口服途径单次应用这些化合物的小鼠的计算致死剂量（LD50）值估计分别为>381、278 和>372mg/kg。化合物 1a 和 1b 显著降低了小鼠的体重增加以及食物和水的摄入。δ-氨基酮戊酸脱水酶（δ-ALA-D）和过氧化氢酶活性在接受化合物 1a 或 1b 最高剂量的小鼠中受到抑制。暴露于化合物 1a、1b 和 1c 并未改变脂质过氧化、维生素 C 水平、大脑 Na(+)/K(+)-ATPase 活性和评估的生化参数。对于药物化学来说，重要的一点是结构修饰不会给小鼠带来毒性。
