Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ejmech.2011.01.020
Title: Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors
Authors: Zhang, C.
Tan, C.
Zu, X.
Zhai, X.
Liu, F.
Chu, B.
Ma, X. 
Chen, Y. 
Gong, P.
Jiang, Y.
Keywords: (S)-3-Aminopyrrolidine
Abl
Dual kinase inhibitor
K562
PI3K
Issue Date: Apr-2011
Citation: Zhang, C., Tan, C., Zu, X., Zhai, X., Liu, F., Chu, B., Ma, X., Chen, Y., Gong, P., Jiang, Y. (2011-04). Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors. European Journal of Medicinal Chemistry 46 (4) : 1404-1414. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejmech.2011.01.020
Abstract: Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition. © 2011 Elsevier Masson SAS. All rights reserved.
Source Title: European Journal of Medicinal Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/105942
ISSN: 02235234
DOI: 10.1016/j.ejmech.2011.01.020
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