Abstract—

The reaction of DL-valine hydroxamic acid with triacetonamine proceeds as the N,N'-regioselective condensation to form (±)-1-hydroxy-3-isopropyl-7,7,9,9-tetramethyl-1,4,8-triazaspiro[4,5]decan-2-one. A study of the antimetastatic and antitumor activities of the resulting hydroxamic acid in vivo by the combined therapy with a cytostatic of the alkylation type on a model of experimental transplanted mouse melanoma B16 showed that the compound is capable of increasing the sensitivity of the tumor to the known antitumor drug cyclophosphamide applied at a subtherapeutic dose. The chemosensitizing activity of hydroxamic acid combined with cyclophosphamide led to an almost twofold increase in the antitumor effect of the cytostatic and a marked decrease in the number of metastases, which showed up as an increase in the metastasis inhibition index (MII) to 74%.

中文翻译：

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基于DL-缬氨酸的环异羟肟酸的区域选择性合成、结构和化学增敏抗肿瘤活性

摘要-

DL-缬氨酸异羟肟酸与三丙酮胺的反应按N , N'-区域选择性缩合形成 (±)-1-羟基-3-异丙基-7,7,9,9-四甲基-1,4,8-三氮杂螺[4,5]癸烷-2-one。在实验性移植小鼠黑色素瘤 B16 模型上，通过与烷基化类型的细胞抑制剂联合治疗所得异羟肟酸在体内的抗转移和抗肿瘤活性研究表明，该化合物能够增加肿瘤对肿瘤的敏感性。已知的抗肿瘤药物环磷酰胺以亚治疗剂量应用。异羟肟酸与环磷酰胺的化学增敏活性导致细胞抑制剂的抗肿瘤作用增加近两倍，转移数量显着减少，转移抑制指数（MII）增加至 74%。