SYNTHESIS AND EVALUTATION OF CATIONIC ANTITUMOR AGENTS

阳离子抗肿瘤剂的合成与评价

• 批准号: 6288049
• 负责人: YUQIANG WANG
• 金额: $ 24.44万
• 依托单位: PANORAMA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6288049
• 关键词: antineoplastics; cations; chemical synthesis; cytotoxicity; drug design /synthesis /production; drug screening /evaluation; laboratory mouse; membrane potentials; neoplastic cell; prodrugs; tissue /cell culture

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.

恶性细胞表现出增加的电负性。 线粒体膜 癌细胞中的潜力高于正常上皮细胞。 这可能是 至少部分负责亲脂性阳离子化合物 有选择地积累在癌细胞中。 我们建议合成和 评估新颖的阳离子（+）-YW-200前药。 （+） - YW-200是一个新的类似物 CC-1065是迄今为止发现的最有效的抗癌药之一。 YW-200是 对不同肿瘤细胞系的阿霉素比阿霉素高1000倍 体外并在体内显示出显着的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，有选择地将 癌细胞，因此具有改善的治疗指数。 拟议的商业应用： 这些新型化合物可以用作抗癌药物。