SOLID TUMOR SELECTIVE COMPOUNDS

本建议侧重于天然药物的合成和生物学评价 和显示实体瘤选择性的非天然类苦木素。 主要 我们的计划的重点是合成quassinoid类似物， 和体内研究，以确定最佳候选人， 进了诊所 此外，该提案还侧重于 海藻素C和甲藻毒素合成。 scytophycins和tolytoxins 然而，尽管是高优先级的， 用于体内评价的候选材料，无可用材料。 一个主要 将致力于探索固体的结构要求， 肿瘤活性 在本补助金申请的第三部分，我们建议 检查了一些卡斯特拉物种（已知含有苦木素的植物） 希望找到丰富的蓝绿石松酮和相关的苦木素来源 更重要的是， 苦木素类以及其他天然产物，这将是实体瘤 选择性的

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.