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.
Keywords: Amide derivatives, Bcr-Abl inhibitors, chronic myeloid leukemia, imatinib, inhibiting activity, molecular docking, SAR.
Letters in Drug Design & Discovery
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.
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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
DOI https://dx.doi.org/10.2174/1570180811666140812231519 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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