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

doi:10.1007/s40242-013-3211-7

Chemical Research in Chinese Universities ›› 2013, Vol. 29 ›› Issue (6): 1104-1109.doi: 10.1007/s40242-013-3211-7

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

SUN Chuan-wen, WANG Jing, PANG Chun-cheng, LI Jing, XIAO Di

College of Life and Environment Sciences, Shanghai Normal University, Shanghai 200234, P. R. China

Received:2013-05-10 Revised:2013-09-25 Online:2013-12-01 Published:2013-10-23
Contact: SUN Chuan-wen E-mail:willin@shnu.edu.cn
Supported by:
Supported by the "Twelfth Five-Year" National Science and Technology Support Program(No.2011BAE06B01-17), the National Natural Science Foundation of China(No.21102092), the Innovation Project of Shanghai Education Commission, China(No.12YZ078) and the Leading Academic Discipline Project of Shanghai Normal University, China(No.DXL123).

Abstract

Abstract:

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 7.51 μg/mL, respectively, which were lower than that of the anticancer drug 5-FU(IC₅₀=8.56 μg/mL). To reduce the toxicity of compounds 3a―3p to the proliferation of normal hematopoietic 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 toxi-city 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 IC₅₀ increased from 35.90 μmol/L to 39.52 μmol/L.

Key words: Tetrahydro-4H-pyrano[3,2-c]pyridine, Leukemia K562 cell, Anti-CD14 monoclonal antibody(McAb), Conjugate, Inhibitory, Toxicity

SUN Chuan-wen, WANG Jing, PANG Chun-cheng, LI Jing, XIAO Di. Synthesis and Anti-leukemia Evaluation of Tetrahydro-4H-pyrano[3, 2-c]pyridines and Corresponding Anti-CD14 Monoclonal Antibody Conjugates[J]. Chemical Research in Chinese Universities, 2013, 29(6): 1104-1109.

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

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