Ma Huan, Chen Gang, Wang Tao, Li Qingeng, Liu Yan
School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
R&D Department, Jiangsu Nhwa Luokang Pharmaceutical Corporation Ltd., Xu Zhou, 221000, China.
Chem Biol Drug Des. 2016 Sep;88(3):363-9. doi: 10.1111/cbdd.12762. Epub 2016 May 24.
The synthesis and preliminary evaluation of derivatives of docetaxel with novel amino acid as a linker named as LK-193˜LK-196 was described. The C2'-modified compound LK-196 behaves as a prodrug; that is, docetaxel is generated upon exposure to human plasma. The compound was also found to have greatly improved water solubility. The pharmacodynamic results showed LK-196 had the self-evident inhibitory effect on tumor growth in vivo, which is a promising candidate for further biological evaluation.
描述了以新型氨基酸为连接基的多西他赛衍生物LK-193至LK-196的合成及初步评价。C2'-修饰的化合物LK-196表现为前药；也就是说，在暴露于人体血浆时会生成多西他赛。还发现该化合物的水溶性有了极大提高。药效学结果表明LK-196在体内对肿瘤生长具有明显的抑制作用，是进一步进行生物学评价的有前景的候选物。
