TUMOR INHIBITORS AND RELATED SUBSTANCES

肿瘤抑制剂及相关物质

• 批准号: 2087818
• 负责人: PAUL A GRIECO
• 金额: $ 29.98万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-06-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2087818
• 关键词: antineoplastics; cardenolides; cardiac glycoside aglycone; chemical structure function; drug adverse effect; drug design /synthesis /production; drug metabolism; drug screening /evaluation; medicinal plants; neoplasm /cancer pharmacology; plant extracts

This proposal focuses on the synthesis of antineoplastic agents. In the quassinoid area major emphasis will be placed on completing syntheses of quassimarin, bruceantin, and glaucarubinone. As a result of the lower toxicity in in vivo systems of 4beta-hydroxy withanolide E relative to cardenolides and bufadienolides, a synthetic program centered around 4beta-hydroxy withanolide E has been initiated in an effort to uncover an analog possessing a reasonable therapeutic index. Part III of this proposal focuses on a convergent total synthesis of the potent cytotoxic cyclodepsidpeptide, jaspamide. In addition a number of analogs will be prepared in order to examine the structural requirements for biological activity.

该提案的重点是抗肿瘤药物的合成。 在 quassinoid 领域，重点将放在完成 quasimarin、bruceantin 和 glaucarubinone 的合成。 作为一个 4β-羟基体内系统毒性较低的结果 醉茄内酯 E 相对于强心烯内酯和蟾蜍二烯内酯，a 以4β-羟基茄内酯E为中心的合成方案 旨在发现具有类似物的 合理的治疗指数。 该提案的第三部分重点 强效细胞毒性物质的聚合全合成 环缩酚肽、贾斯帕酰胺。 此外还有一些类似物 将准备好检查结构要求 用于生物活性。