SYNTHESIS AND EVALUTATION OF CATIONIC ANTITUMOR AGENTS

恶性细胞的电负性增强。线粒体膜 癌细胞的潜伏期高于正常上皮细胞。这可能是 至少部分原因是亲脂性阳离子化合物 选择性地积聚在癌细胞中。我们建议合成和合成 评价新型阳离子()-YW-200前药。()-YW-200是一种新的模拟 CC-1065，迄今为止发现的最有效的抗癌药物之一。YW-200是 对不同肿瘤细胞株的杀伤能力是阿霉素的1000倍 在体外表现出显著的体内抗肿瘤活性，而不会引起 骨髓抑制，其他CC-1065类似物的剂量限制毒性。新的 阳离子()-YW-200前药将是水溶性的，可选择性地被 癌细胞，因此有一个改善的治疗指数。 建议的商业应用： 这些新化合物可用作抗癌药物。

Malignant cells exhibit increased electronegativity. The mitochondrial membrane potential is higher in carcinoma cells than in normal epithelial cells. This may be at least partially responsible for the fact that lipophilic cationic compounds selectively accumulate in carcinoma cells. We propose to synthesize and evaluate novel cationic (+)- YW-200 prodrugs. (+)-YW-200 is a new analog of CC-1065, one of the most potent anticancer drug discovered to date. YW-200 is 1000-fold more potent than doxorubicin against different tumor cell lines in vitro and shows remarkable antitumor activity in vivo without causing myelosuppression, the dose-limiting toxicity of other CC-1065 analogs. The new cationic (+)-YW-200 prodrugs will be water-soluble, selectively taken-up by cancer cells, and thus have an improved therapeutic index. PROPOSED COMMERCIAL APPLICATION: These novel compounds can be used as anticancer drugs.