Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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

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

Graphical Abstract:


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.

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Article Details

VOLUME: 12
ISSUE: 1
Year: 2015
Page: [20 - 28]
Pages: 9
DOI: 10.2174/1570180811666140812231519