Design, Synthesis and Cytotoxic Evaluation of Novel Imatinib Amide Derivatives that Target Abl Kinase

Title:Design, Synthesis and Cytotoxic Evaluation of Novel Imatinib Amide Derivatives that Target Abl Kinase

Volume: 12 Issue: 1

Author(s): Ri-Sheng Yao, Qiu-Xiang Guan, Xiao-Qin Lu and Ban-Feng Ruan

Affiliation:

Keywords: Amide derivatives, Bcr-Abl inhibitors, chronic myeloid leukemia, imatinib, inhibiting activity, molecular docking, SAR.

Abstract: Novel imatinib amide derivatives (a1-28, b1-9) were synthesized and evaluated for their biological activities. All compounds were characterized by ¹H NMR, MS and elemental analysis. Among all the derivatives, compounds a4, a10, a21, b1 and b2 displayed the most significant ability of inhibiting K562 cell proliferation with the IC₅₀ values of 0.67, 0.66, 0.65, 0.59 and 0.62 µM, respectively, indicating that these compounds were potent inhibitors of Bcr-Abl in leukemic K562 cells, comparable to the reference compound imatinib. Molecular docking study was performed to position compounds a21 and b1 into the active site of Abl to determine the probable binding modes.

Cite this article as:

Yao Ri-Sheng, Guan Qiu-Xiang, Lu Xiao-Qin and Ruan Ban-Feng, Design, Synthesis and Cytotoxic Evaluation of Novel Imatinib Amide Derivatives that Target Abl Kinase, Letters in Drug Design & Discovery 2015; 12 (1) . https://dx.doi.org/10.2174/1570180811666140812231519