芳基噻唑烷酰胺作为黑色素瘤选择性细胞毒剂的构效关系研究
Structure-activity relationship studies of arylthiazolidine amides as selective cytotoxic agents for melanoma.
作者信息
Li Wei, Wang Zhao, Gududuru Veeresa, Zbytek Blazej, Slominski Andrzej T, Dalton James T, Miller Duane D
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
出版信息
Anticancer Res. 2007 Mar-Apr;27(2):883-8.
UNLABELLED
New drugs are urgently needed for improved therapy for melanoma.
MATERIALS AND METHODS
Ninety-one novel compounds were evaluated in two melanoma and one normal skin cell lines to identify potential lead compounds with high potency and selectivity. Mechanisms of action for the best compound were also investigated.
RESULTS
Three potent lead structures (serine amino alcohols, serine amides and thiazolidines) were identified, with thiazolidines having both excellent potency and high selectivity when compared with sorafenib, a drug used extensively in clinical trials for melanoma. Analyzing the effect of the lead compound showed that it induced DNA degradation consistent with necrotic cell death.
CONCLUSION
The lead structure represents a novel class of compounds that can be further optimized for potential drug to treat advanced melanoma.
未标记
黑色素瘤的治疗急需新型药物。
材料与方法
在两种黑色素瘤细胞系和一种正常皮肤细胞系中评估了91种新型化合物，以鉴定具有高效能和高选择性的潜在先导化合物。还研究了最佳化合物的作用机制。
结果
鉴定出三种有效的先导结构（丝氨酸氨基醇、丝氨酸酰胺和噻唑烷），与索拉非尼相比，噻唑烷具有优异的效能和高选择性，索拉非尼是一种在黑色素瘤临床试验中广泛使用的药物。分析先导化合物的作用表明，它诱导了与坏死性细胞死亡一致的DNA降解。
结论
先导结构代表了一类新型化合物，可进一步优化以开发治疗晚期黑色素瘤的潜在药物。
Zotero 插件