SOLID TUMOR SELECTIVE COMPOUNDS

实体肿瘤选择性化合物

• 批准号: 6375628
• 负责人: PAUL A GRIECO
• 金额: $ 24.16万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 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 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6375628
• 关键词: analog; antineoplastics; cardenolides; cardiac glycoside aglycone; cytotoxicity; drug design /synthesis /production; drug screening /evaluation; heterocyclic polycyclic compound; neoplasm /cancer pharmacology; plant extracts

This proposal focuses on the synthesis and biological evaluation of natural and unnatural quassinoids which display solid tumor selectivity. The major thrust of our program is the synthesis of quassinoid analogs for in vitro and in vivo studies in order to define the best candidate to move forward into the clinic. In addition this proposal concentrates on the total synthesis of scytophycin C and tolytoxin. The scytophycins and tolytoxins are solid tumor selective in vitro, however, despite being high priority candidates for in vivo evaluation, no material is available. A major effort will be devoted to probing the structural requirements for solid tumor activity. In part III of this grant application we propose to examine a number of Castela species (plants known to contain quassinoids) in hopes of finding a rich source of glaucarubolone and related quassinoids for our analog program and, more importantly, identifying novel cytotoxic quassinoids as well other natural products which will be solid tumor selective.

本方案的重点是天然产物的合成和生物学评价。 以及具有固体肿瘤选择性的非天然类喹乙醇。少校 我们计划的主要内容是体外合成四氢喹啉类似物。 和活体研究，以确定最好的候选者 送进诊所。此外，这项建议集中在总额上 镰刀菌素C和溶毒素的合成。镰刀菌素和溶血毒素 然而，实体瘤在体外是有选择性的，尽管是高度优先的 对于活体评估的候选者，目前还没有材料可用。一位少校 将致力于探索Solid的结构要求 肿瘤活动性。在这项拨款申请的第三部分，我们建议 检查一些蓖麻属物种(已知含有藜芦素的植物) 希望找到丰富的蓝藻红素和相关的Quassinoid来源 对于我们的模拟程序，更重要的是，识别新的细胞毒性 Quassinoid以及其他天然产物会成为实体肿瘤 有选择性的。

项目成果

Quassinoids from the twigs and thorns of Castela polyandra.

• DOI: 10.1016/s0031-9422(98)00589-5
• 发表时间: 1999-02
• 期刊: Phytochemistry
• 影响因子: 3.8
• 作者: P. Grieco;Jalal Haddad;M. Pineiro-Nunez;John C. Huffman

Non-quassinoid constituents from the twigs and thorns of Castela polyandra.

来自多花古香的嫩枝和刺的非苦木素成分。

• DOI: 10.1016/s0031-9422(99)00060-6
• 发表时间: 1999
• 期刊: Phytochemistry
• 影响因子: 3.8
• 作者: Grieco,PA;Haddad,J;Piñeiro-Núñez,MM;Huffman,JC
• 通讯作者: Huffman,JC

Baeyer-Villiger oxidation promoted by reaction of peracids with cyclic oxocarbenium ions generated in situ from internal hemiketals.

过酸与内部半缩酮原位生成的环状氧碳鎓离子反应促进了拜尔-维利格氧化。

• DOI: 10.1021/ol000068j
• 发表时间: 2000
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Hunt,KW;Grieco,PA
• 通讯作者: Grieco,PA

Polyandrol, a C19 quassinoid from Castela polyandra.

• DOI: 10.1016/0031-9422(94)00817-d
• 发表时间: 1995-04
• 期刊: Phytochemistry
• 影响因子: 3.8
• 作者: P. Grieco;J. M. Vander Roest;M. Pineiro-Nunez;E. Campaigne;M. Carmack