A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, in

• 作 者: Xiaoyi Zhang Yifan Yang Ming Zhao Liu Liu Meiqing Zheng Yuji Wang Jianhui Wu Shiqi Peng
• 机 构: College of Pharmaceutical Sciences, Capital Medical University, No.10, Beijing 100069, PR China
• 出 处: 首都医科大学2013年研究生学术论坛
• 发表日期: 2013年2期

　　From the anti-tumor active N-tryptophanyl-b-carboline-3-carboxylic acid benzyl ester and b-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-AAOBzls (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.