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.

该提案着重于自然的综合和生物学评估 以及表现出实体肿瘤选择性的不自然的Quassinoid。 专业 我们程序的推力是用于体外类似物的合成 和体内研究，以定义前进的最佳候选人 进入诊所。 另外，该提议集中于总数 Scytophycin C和甲毒素的合成。 Scytophophincins和Tolytoxins 尽管优先级很高，但在体外选择性选择性 体内评估的候选人，没有任何材料可用。 专业 努力将致力于探测固体的结构要求 肿瘤活性。 在本赠款申请的第三部分中，我们建议 检查许多Castela物种（已知包含木材的植物） 希望找到丰富的glaucarubolone和相关的木制来源 对于我们的模拟程序，更重要的是，识别新型的细胞毒性 木工以及其他将是实体瘤的天然产品 选择性。

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