Synthesis and Anti-leukemia Evaluation of Tetrahydro-4H-pyrano[3,2-c]pyridines and Corresponding Anti-CD14 Monoclonal Antibody Conjugates  

作　　者：SUN Chuan-wen WANG Jing PANG Chun-cheng LI Jing XIAO Di 

机构地区：[1]College of Life and Environment Sciences, Shanghai Normal University, Shanghai 200234, P.R.China

出　　处：《Chemical Research in Chinese Universities》2013年第6期1104-1109,共6页高等学校化学研究（英文版）

基　　金：the ＂Twelfth Five-Year＂ National Science and Technology Support Program，the National Natural Science Foundation of China，the Innovation Project of Shanghai Education Commission,China，the Leading Academic Discipline Project of Shanghai Normal University,China

摘　　要：A series of novel tetrahydro-4H-pyrano[3,2-c]pyridines（3a-3p） were synthesized and found to possess potent antiproliferative activity against leukemia K562 cells in vitro. Preliminary bioassay indicates that compounds 3a and 3e afford the best activity, the IC50 values of them were 6.93 and 7.51μg/mL, respectively, which were lower than that of the anticancer drug 5-FU（1C50=8.56μg/mL）. To reduce the toxicity of compounds 3a-3p to the prolife- ration of normal bematopoietic cells, a tumor targeted CD14 monoclonal antibody（McAb） was used in conjugation with compounds 3a--3p to get conjugates 4a--4p, respectively. The inhibitory activities of conjugates 4a--4p toward K562 cells were discovered to approach those of compounds 3a--3p. In the presence of CD14 McAb, tumor cells were found to be much more susceptible to conjugates 3a--3p than normal hematopoietic cells. Therefore, the toxicity of conjugates 4a--4p to normal hematopoietic cells declined obviously. For example, as for the toxicity of compound 3a compared with that of compound 4a, the value of ICs0 increased from 35.90 μmol/L to 39.52 μmol/L.A series of novel tetrahydro-4H-pyrano[3,2-c]pyridines（3a-3p） were synthesized and found to possess potent antiproliferative activity against leukemia K562 cells in vitro. Preliminary bioassay indicates that compounds 3a and 3e afford the best activity, the IC50 values of them were 6.93 and 7.51μg/mL, respectively, which were lower than that of the anticancer drug 5-FU（1C50=8.56μg/mL）. To reduce the toxicity of compounds 3a-3p to the prolife- ration of normal bematopoietic cells, a tumor targeted CD14 monoclonal antibody（McAb） was used in conjugation with compounds 3a--3p to get conjugates 4a--4p, respectively. The inhibitory activities of conjugates 4a--4p toward K562 cells were discovered to approach those of compounds 3a--3p. In the presence of CD14 McAb, tumor cells were found to be much more susceptible to conjugates 3a--3p than normal hematopoietic cells. Therefore, the toxicity of conjugates 4a--4p to normal hematopoietic cells declined obviously. For example, as for the toxicity of compound 3a compared with that of compound 4a, the value of ICs0 increased from 35.90 μmol/L to 39.52 μmol/L.

关 键 词：Tetrahydro-4H-pyrano[3 2-c]pyridine Leukemia K562 cell Anti-CDl4 monoclonal antibody（McAb） Conjugate Inhibitory Toxicity 

分 类 号：TQ655[化学工程—精细化工] S852.43[农业科学—基础兽医学]