REPRODUCTIVE TOXICOLOGY OF BORON ANALOGS OF BIOMOLECULES

生物分子中的硼类似物显示出相当大的治疗潜力 在癌症治疗领域，骨病(如骨质疏松症)， 高脂血症和炎症。已经有相当多的活动 在细胞培养和啮齿动物模型中进行了演示。大多数特工 急性毒性测试似乎是安全的。然而，考虑到 硼酸(及其硼酸盐)的生殖和内分泌毒性， 重要的是要确定生物分子中的硼类似物 表现出类似的毒性。 第一阶段的研究将集中在合成方法的开发(TO 生产大量用于毒性研究的材料)、开发 用于确定睾丸和内分泌影响的生物检测方法，以及 使用新开发的生物检测方法筛选化合物。 在第二阶段的研究中，化合物将被测试内分泌损伤，使用 内分泌快速生物测定法及其相对重要性的确定 用于药物开发。这些毒性信息，与 已经观察到的药理活性，将使我们能够 继续开发具有药理活性的硼化合物。

Boron analogs of biomolecules exhibit considerable therapeutic potential in the areas of cancer treatment, bone disorder (such as osteoporosis), hyperlipidemia and inflammation. Considerable activity has been demonstrated in cell cultures and rodent models. Most of the agents tested for acute toxicity appear to be safe. Considering, however, the reproductive and endocrine toxicity of boric acid (and its borate salts), it its important to determine whether boron analogs of biomolecules exhibit similar toxicity. The Phase I studies will focus on synthetic methods development (to produce large quantities of materials for toxicity studies), development of bioassays for determining testicular and endocrine effects, and screening of compounds using the newly developed bioassays. In Phase II studies, compounds will be tested for endocrine lesions using the rapid endocrine bioassay and to determine their relative importance for drug development. This toxicity information, combined with the pharmacological activity already observed, will then enable us to continue the development of pharmacologically active boron compounds.