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

Meiqing Zheng, Yifan Yang, Ming Zhao, Xiaoyi Zhang, Jianhui Wu, Gong Chen, Li Peng, Yuji Wang, Shiqi Peng

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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 × 10-8 M and 6 × 10-7 M, respectively. On S180 mice model 100 μmol/kg of 3a-r effectively inhibited the growth of the tumors. Using MFA based Cerius2 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.

Original languageEnglish (US)
Pages (from-to)1672-1681
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number5
DOIs
StatePublished - May 1 2011

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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