Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.bmc.2009.09.008
Title: Synthesis and evaluation of functionalized isoindigos as antiproliferative agents
Authors: Wee, X.K.
Yeo, W.K. 
Zhang, B. 
Tan, V.B.C. 
Lim, K.M. 
Tay, T.E. 
Go, M.-L. 
Keywords: Antiproliferative activity
CDK2 inhibition
Isoindigo
Molecular modeling
SAR
Issue Date: 1-Nov-2009
Source: Wee, X.K., Yeo, W.K., Zhang, B., Tan, V.B.C., Lim, K.M., Tay, T.E., Go, M.-L. (2009-11-01). Synthesis and evaluation of functionalized isoindigos as antiproliferative agents. Bioorganic and Medicinal Chemistry 17 (21) : 7562-7571. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bmc.2009.09.008
Abstract: A series of functionalized isoindigos structurally related to meisoindigo (1-methylisoindigo), a therapeutic agent used for the treatment of a form of leukemia, were synthesized and evaluated for antiproliferative activities on a panel of human cancer cells. Two promising compounds (1 -phenpropylisoindigo and 1-(p-methoxy-phenethyl)-isoindigo) that were more potent than meisoindigo and comparable to 6bromoindirubin-3'-oxime on leukemic K562 and liver HuH7 cells were identified. Structure-activity relationships showed the importance of keeping one of the lactam NH in an unsubstituted state. Substitution of the other lactam NH with aryl or arylalkyl side chains retained or improved activity in most instances. An intact exocyclic double bond was also essential, possibly to maintain planarity and rigidity of the isoindigo scaffold. None of the compounds were found to inhibit CDK2 in an in vitro assay, in spite of reports linking the antiproliferative activities of meisoindigo and other isoindigos to CDK2 inhibition. Hence, these functionalized isoindigos disrupted cell growth and proliferation by other mechanistic pathways that did not involve CDK2 inhibition. © 2009 Elsevier Ltd. All rights reserved.
Source Title: Bioorganic and Medicinal Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/51531
ISSN: 09680896
DOI: 10.1016/j.bmc.2009.09.008
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