Antifertility potential of ornidazole analogues in rats.
Antifertility potential of ornidazole analogues in rats.
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奥硝唑类似物对大鼠的抗生育潜力。
DOI：
10.1002/j.1939-4640.1997.tb01949.x
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发表时间：
1997
影响因子：
--
通讯作者：
Günter Haufe
中科院分区：
文献类型：
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作者：
Trevor G. Cooper;C. Yeung;Rolf Skupin;Günter Haufe
为了确定奥硝唑分子[1-（3-氯-2-羟基）丙基-2-甲基-5-硝基咪唑]的哪一部分负责其抗生育作用，将结构类似物以相当于奥硝唑抗生育剂量（1.82 mmol/kg/天）的剂量喂给已证实具有生育能力的雄性大鼠。在经口灌胃（对照交配）前以及饲喂10天和14天后，通过计数交配后12天雌性动物中存在的胎仔和黄体数量，检测雄性动物的生育力。在最后一次交配后的第二天，用Hamilton-Thorne运动分析仪客观地评估了附睾尾精子的运动学参数。咪唑环上带有2-硝基和5-甲基的类似物如果（氯羟基）丙基被质子或甲基、羟乙基、氯乙基或（磺酰基乙基）乙基取代则无活性，表明奥硝唑的三碳侧链是抗生育作用所必需的。只有奥硝唑及其醋酸盐是有效的抗生育药物，但带有（氯羟基）丙基侧链连接到杂环邻苯二甲酰亚胺的氮原子的化合物产生了部分但暂时的生育能力降低。奥硝唑的作用与男性抗生育剂，α-氯醇[3-氯-1，2-丙二醇]的相似性，进行了讨论。
In order to determine which part of the ornidazole molecule [1-(3-chloro-2-hydroxy)propyl-2-methyl-5-nitroimidazole] is responsible for its antifertility action, structural analogues were fed to male rats of proven fertility at doses equivalent to the antifertility dose of ornidazole (1.82 mmol/kg/day). The fertility of the males was tested, before oral gavage (control mating) and after 10 and 14 days of feeding, by counting the number of fetuses and corpora lutea present in females 12 days after mating. The day after the last mating, the kinematic parameters of sperm from the cauda epididymidis were assessed objectively with a Hamilton-Thorne motility analyzer. Analogues bearing the 2-nitro and 5-methyl groups on the imidazole ring were inactive if the (chlorohydroxy)propyl group were substituted by proton or methyl, hydroxyethyl, chloroethyl, or (sulfonylethyl)ethyl groups, indicating that the three-carbon side chain of ornidazole was necessary for the antifertility action. Only ornidazole and its acetate were effective antifertility agents, but a compound bearing the (chlorohydroxy)propyl side chain attached to a nitrogen atom of a heterocyclic phthalimide produced a partial but temporary reduction in fertility. Similarities of the action of ornidazole with the male antifertility agent, alpha-chlorohydrin [3-chloro-1,2-propanediol], are discussed.