Abstract
A series of Schiff bases derived from 4-methylsalicylic acid (4a–4s) were synthesized, 14 of which (4a–4h, 4j–4l, 4n, 4q, and 4s) were reported for the first time. All the synthesized compounds were evaluated for their immunosuppressive activities for the first time. Among them, compound 4o displayed the most potent biological activity against lymph node cells (IC50 = 1.02 μM for lymph node cells and IC50 = 2.17 μM for PI3Kγ). The results of apoptosis and western-blot assays demonstrated that the immunosuppressive activity of compound 4o might be mediated by the inhibition of PI3K/AKT signaling pathway. Docking simulation was performed to position compound 4o into the PI3Kγ structure active site to determine the probable binding model.
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The study was financed by National Natural Science Foundation of China (No. J1103512).
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Ru Yan and Peng-Gang Liu equally contributed to this paper.
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Yan, R., Liu, PG., Zhang, ZM. et al. Synthesis, biological evaluation and molecular modeling studies of Schiff bases derived from 4-methylsalicylic acid as potential immunosuppressive agents. Med Chem Res 22, 5707–5716 (2013). https://doi.org/10.1007/s00044-013-0561-0
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DOI: https://doi.org/10.1007/s00044-013-0561-0