TY - JOUR
T1 - A class of novel N-isoquinoline-3-carbonyl-l-amino acid benzylesters
T2 - Synthesis, anti-tumor evaluation and 3D QSAR analysis
AU - Zheng, Meiqing
AU - Yang, Yifan
AU - Zhao, Ming
AU - Zhang, Xiaoyi
AU - Wu, Jianhui
AU - Chen, Gong
AU - Peng, Li
AU - Wang, Yuji
AU - Peng, Shiqi
N1 - Funding Information:
This work was completed in the Beijing area major laboratory of peptide and small molecular drugs, supported by PHR (IHLB, KZ 200810025010 ), the National Natural Scientific Foundation of China ( 20772082, 30801426, 30901843 ), and Special Project ( 2008ZX09401-002 ) of China.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ejmech.2011.02.017
DO - 10.1016/j.ejmech.2011.02.017
M3 - Article
C2 - 21414693
AN - SCOPUS:79953168361
SN - 0223-5234
VL - 46
SP - 1672
EP - 1681
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 5
ER -