Chemoprevention of Lung Cancer by myo Inositol Analogs

环醇、肌醇及其相应的六磷酸盐(IP6)是一种很有前途的抗癌药物。由于代谢不稳定，活性化合物的结构及其对细胞功能的影响尚不清楚。有人认为，肌醇磷酸盐作为生物上重要的信号分子，对观察到的化学预防活性起到了作用。使用成熟的化学方法，我们打算用代谢稳定的类似物来模拟这些化合物。这些类似物对经过肺部特异性致癌物处理的正常小气道上皮(SAE)细胞的作用将被表征。将确定与肌醇信号相关的细胞事件的相对活性和变化(即，钙动员)。我们打算定义肌醇化合物对致癌物暴露的SAE细胞的影响的结构框架，并确定显示出增强抑制肺癌能力的药物。

The cyclitol myo-inositol and its corresponding hexaphosphate (IP6) are promising agents for cancer prevention. Due to metabolic instability, the structure of the active compound or compounds and their influence on cellular function are unknown. It is proposed that inositol phosphates that serve as biologically important signaling molecules are responsible for the observed ` chemopreventive activity. Using well- established chemical methods, we intend to mimic these compounds with metabolically stable analogs. The action of the analogs on normal small airway epithelial (SAE) cells that have been treated with lung- specific carcinogens will be characterized. Relative activity and changes in cellular events linked to inositol signaling (i.e., Ca2+ mobilization) will be determined. We intend to define a structural framework for the influence of inositol compounds on carcinogen- exposed SAE cells and identify agents that display an enhanced aptitude for the suppression of lung cancer.