A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

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

来源：European Journal of Medicinal Chemistry, 2011, 46(8): 3410-3419.

DOI：10.1016/j.ejmech.2011.05.004

• Trp-Trp-AA-OBzl
• Anti-tumor
• Intercalation
• Docking
• 3D QSAR

From the anti-tumor active N-tryptophanyl-beta-carboline-3-carboxylic acid benzyl ester and beta-carboline-3-carbonyltryptophan benzyl ester, a pharmacophore, Trp-Trp-OBzl, was drawn. Based on the DOCK scores amino acid residue was inserted into the C-terminus of Trp-Trp-OBzl and twenty Trp-Trp-AA-OBzls (AA = amino acid residues) were provided as DNA intercalators. On the in vitro and in vivo models seventeen Trp-Trp-AA-OBzls were anti-tumor active, and twelve Trp-Trp-AA-OBzls were more active than cytarabine. In acute toxicity assay Trp-Trp-AA-OBzls did not damage the immunologic function and had an LD50 of more than 500 mg/kg. The relationships of structure and activity were analyzed with 3D QSAR The action mechanism studies revealed that the in vivo anti-tumor action of Trp-Trp-AA-OBzls was the result of DNA intercalation.

• 出版日期2011-8
• 单位首都医科大学