A class of novel N-isoquinoline-3-carbonyl-L-amino acid benzylesters: Synthesis, anti-tumor evaluation and 3D QSAR analysis

作者：Zheng, Meiqing; Yang, Yifan; Zhao, Ming; Zhang, Xiaoyi; Wu, Jianhui; Chen, Gong; Peng, Li; Wang, Yuji; Peng, Shiqi^*

来源：European Journal of Medicinal Chemistry, 2011, 46(5): 1672-1681.

DOI：10.1016/j.ejmech.2011.02.017

• N-Isoquinoline-3-carbonylamino acid benzylester
• Intercalator
• Anti-tumor
• 3D QSAR
• Membrane permeability

Isoquinoline-3-carboxylic acid (2) was modified with amino acid benzylesters and 18 novel N-isoquinoline-3-carbonylamino acid benzylesters (3a-r) were provided. The IC50 values of 3a-r against the proliferation of HL-60 and Hela cells were less than 1 x 10(-8) M and 6 x 10(-7) M, respectively. On S180 mice model 100 mu mol/kg of 3a-r effectively inhibited the growth of the tumors. Using MFA based Cerius(2) QSAR module, two equations (r, 0.989 and 0.987) were established to correlate the structure with the in vitro and in vivo activities. The benefit of this modification was supported with both the in vitro membrane permeation test and the in vivo anti-tumor assay. The in vitro membrane permeability of N-isoquinoline-3-carbonyl-L-threonine benzylester (3n) and N-isoquinoline-3-carbonyl-L-leucine benzylester (3q) was 2.5 fold higher than that of 2, and the in vivo anti-tumor activity of 3n, q was 4.4-fold higher than that of 2.

• 出版日期2011-5
• 单位首都医科大学